Induced stem cells
Induced stem cells (iSC) are stem cells artificially derived from some other (somatic, reproductive, pluripotent etc.) cell types by induced (i.e. initiated, forced) epigenetic reprogramming. In accordance to the developmental potentiality and the degree of cell dedifferentiation caused by induced reprogramming they are distinguished and subdivided as: induced totipotent, induced pluripotent stem cells (iPSc) and, obtained by so-called direct reprogramming or directed forced differentiation, induced progenitor (multipotent or unipotent) stem cells, also called induced somatic stem cells. Currently, there are three ways to reprogram somatic cells into stem cells These are:
- Transplantation of nuclei taken from somatic cells into a fertilized egg or oocyt from which the nucleus is removed prior
- Fusion of somatic cells with pluripotent stem cells and
- Modification of somatic cells, inducing its transformation into a stem cell, using: the genetic material encoding reprogramming protein factors,,; recombinant proteins; microRNA, a synthetic, self-replicating polycistronic RNA and low-molecular biologically active substances.
- 1 Metaplasia and Transdetermination - natural processes of induction
- 2 Induced totipotent cells and their use for cloning and generation of genetically modified animals
- 3 iPSc as a result of radical rejuvenation
- 3.1 Chemically induced pluripotent cells (CiPSCs)
- 3.2 Method for producing cells induced to differentiate from iPSCs in the teratoma under in vivo conditions
- 3.3 Cell therapy with retina cells obtained from iPSCs
- 3.4 Generation of lung and airway epithelial cells from iPSC
- 3.5 Differentiation of iPSCs into reproductive cells
- 4 Induced progenitor stem cells
- 4.1 Methods of direct transdifferentiation
- 4.2 Reprogramming by means of a phased process modeling regeneration
- 4.3 Transdifferentiation by using an antibody
- 4.4 Conditionally reprogrammed cells (CRCs)
- 4.5 Indirect lineage conversion (ILC)
- 4.6 Reprogramming induced by the influence on the outer membrane glycoprotein
- 4.7 Reprogramming through a physical approach
- 4.8 Induced neural stem cells (iNSCs)
- 4.9 Oligodendrocyte precursor cells (OPCs)
- 4.10 Induced cardiomyocytes (iCMs)
- 4.11 Direct Reprogramming of Adult Cells to Nephron Progenitors (iNP)
- 4.12 Bioengineering of the cells of blood vessels
- 4.13 Bioengineering of blood stem cells
- 4.14 Induced Mesenchymal stem cells (iMSCs)
- 4.15 Induced chondrogenic cells (iChon cells)
- 5 Sources of cells for reprogramming
- 6 Notes
- 7 References
- 8 Notes
Metaplasia and Transdetermination - natural processes of induction
The reversible transformation of one differentiated cell type to another type of mature differentiated cells is called metaplasia. This transition from one cell type to another can be a part of the normal maturation process, or caused by some of its inducing stimulus. For example: transformation of cells of the iris to the lens in the process of maturation and transformation of the retinal pigment epithelium cells into the neural retina during regeneration in adult newt eyes. This process allows the body to replace the original cells not suitable to new conditions, into new cells which are more suited to new conditions. In experiments on cells in Drosophila imaginal discs, it was found that there are a limited number of standard discrete states of differentiation and the cells have to choose one of them. The fact that transdetermination (change of the path of differentiation) often take place not in one, but in a group of cells shows that it is not caused by a mutation but is induced.
Some types of mature, specialized adult cells can naturally revert to stem cells. For example, differentiated cells, which are called chief cells and express the stem cell marker Troy, normally produce digestive fluids for the stomach, yet they can change back into stem cells to make temporary repairs in significant stomach injuries, such as a cut or damage from infection. Moreover they’re making this transition even in the absence of noticeable injuries and are capable of replenishing entire gastric units, essentially serving as quiescent “reserve” stem cells. Differentiated airway epithelial cells can revert into stable and functional stem cells in vivo. After injury, mature terminally differentiated kidney cells dedifferentiate into more primordial versions of themselves, and then differentiate into the cell types needing replacement in the damaged tissue Macrophages can self-renew by local proliferation of mature differentiated cells. In Newts, muscle tissue is regenerated from specialized muscle cells that dedifferentiate and forget what type of cell they've been. This capacity to regenerate tissue does not decline with age, which may be linked to their ability to make new stem cells from muscle cells on demand.
It should be noted that there are also a variety of nontumorigenic stem cells with the ability to generate the multiple cell types. For instance, multilineage-differentiating stress-enduring (Muse) cells are the stress-tolerant adult human stem cells that can self-renew; form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency; and can differentiate into endodermal, ectodermal, and mesodermal cells both in vitro and in vivo.
Induced totipotent cells and their use for cloning and generation of genetically modified animals
Induced totipotent cells usually can be obtained by reprogramming somatic cells by somatic-cell nuclear transfer (SCNT) to the recipient eggs or oocytes. Sometimes may be used the oocytes of other species, such as sheep. New possibilities for creating genetically modified animals opens method of induced androgenetic haploid embryonic stem cells, which can be used instead of sperm. These cells, synchronized in M phase and injected into the oocyte allow to get viable offspring. These developments, together with data on the possibility to obtain unlimited number of oocytes from mitotically active reproductive stem cells offer the possibility of industrial production of transgenic farm animals. Repeated recloning of viable mice through a somatic cell nuclear transfer method that includes a histone deacetylase inhibitor – trichostatin, added to the cell culture medium, show that it may be possible to reclone animals indefinitely without any visible accumulation of reprogramming or genomic errors  However, research into technologies to develop sperm and egg cells from stem cells bring up bioethical issues.
Such technologies may also have far-reaching clinical applications for overcoming cytoplasmic defects in human oocytes. For example, the technology have been developed that could prevent inherited mitochondrial disease being passed on to the next generation. Mitochondria, often described as the powerhouse of the cell, contain genetic material, which is passed from mother to child. Mutations on mitochondrial DNA can cause diabetes, deafness, eye disorders, gastrointestinal disorders, heart disease, dementia and several other neurological diseases. The nucleus from one human egg cell have been transferred to another egg, effectively swapping the cell cytoplasm, which includes the mitochondria (and their DNA), creating a cell that could be regarded as having two mothers. The eggs were then fertilised, and the resulting embryonic stem cells carried the swapped mitochondrial DNA.
Read more about the latest achievements of the cloning techniques and the generation of totipotent cells, in:
iPSc as a result of radical rejuvenation
See also main article: induced pluripotent stem cells (iPSc)
First iPSc were obtained in the form of transplantable teratocarcinoma induced by the graft taken from mouse embryos. It was shown that teratocarcinoma formed from somatic cells. The fact that normal genetically mosaic mice can be obtained from malignant teratocarcinoma cells confirmed their pluripotency. It turned out that teratocarcinoma cells are able to maintain a culture of pluripotent embryonic stem cells in an undifferentiated state, by supplying the culture medium with various factors. Thus, as early as in the 1980s, it became clear that the transplantation of pluripotent or embryonic stem cells into the body of adult mammals, usually leads to the formation of teratomas, which can then turn into a malignant tumor teratocarcinoma. If, however, to put the teratocarcinoma cells into the early mammal embryo (at the blastocyst stage), they became incorporated in the cell mass of blastocysts and from such a chimeric (i.e. composed of cells from different organisms) blastocyst often develops normal chimeric animal. This indicated that the cause of the teratoma is a dissonance - mutual misunderstanding of "speech" of young donor cells and surrounding adult cells (so-called niche) of the recipient.
In August 2006, Japanese researchers circumvented the need for an oocyte, which is required for SCNT-mediated nuclear reprogramming method. By reprograming mouse embryonic fibroblasts into pluripotent stem cell via the ectopic expression of only four transcription factors, namely Oct4, Sox2, Klf4 and c-Myc, they proved that the overexpression of a surprisingly small number of factors can sometimes push the cell to transition to a new stable state that is associated with changes in the activity of thousands of genes. The properties of IPSC were very similar to embryonic stem cells (ESCs). iPSCs have been shown to support the development of all-iPSC mice using tetraploid (4n) embryo, the most stringent assay for developmental potential. However, some genetically normal iPSCs failed to give rise to all-iPSC mice on the score of aberrant epigenetic silencing of the imprinted Dlk1-Dio3 gene cluster. An important advantage of iPSC to ESC is that they can be derived from adult cells, rather than from embryos. Therefore, it became possible to obtain iPSC from adults and even elderly patients Reprogramming of somatic cells to iPSC leads to rejuvenation. It was found that reprogramming to iPSC leads to telomere lengthening and shortening after their subsequent differentiation back into fibroblast-like derivatives. Thus, reprogramming of somatic cells to iPSC leads to the restoration of embryonic telomere length, and hence increases the potential number of cell divisions limited by Hayflick limit,. Therefore, technology of iPSC should be seen as a radical way to rejuvenation. Unfortunately, because of the dissonance between rejuvenated cells and their surrounding (so-called niche ) of older cells of the recipient, the injection of the patient by his own iPSC, usually leads to an immune response, which can be used for medical purposes, or the formation of tumors such as teratoma. The reason for this probably lies in the fact that some cells differentiated from ESC and iPSC in vivo continue to synthesize the embryonic isoforms of protein. So, the immune system might detect and attack cells that are not cooperating properly.
Hope gives us study which showed that a small molecule called MitoBloCK-6 can force the pluripotent stem cells to die by triggering apoptosis (via cytochrome c release across the mitochondrial outer membrane in human pluripotent stem cells but not in differentiated cells), while shortly after differentiation their daughter cells became resistant to death. When MitoBloCK-6 introduced to differentiated cell lines, the cells remained healthy. The key to the survival of the differentiated cells, when the cells are exposed to MitoBloCK-6, may be due to the changes undergone by pluripotent stem cell mitochondria in the process of cell differentiation. This ability of MitoBloCK-6 to separate the pluripotent and differentiated cell lines could potentially reduce the risk of teratomas and other problems in regenerative medicine treatment strategies. Recently been identified others small molecules (selective cytotoxic inhibitors of hPSCs) that prevented human pluripotent stem cells from forming teratomas in mice following transplantation. The most potent and selective compound of them (PluriSIn #1) inhibits stearoyl-coA desaturase (the key enzyme in oleic acid biosynthesis), which finally results in apoptosis. With the help of this molecule the undifferentiated cells can be selectively removed from culture. An efficient strategy to selectively eliminate pluripotent cells with teratoma potential is targeting pluripotent stem cell-specific antiapoptotic factor(s) (i.e., survivin or Bcl10). Indeed, a single treatment of mixed population with chemical inhibitors of survivin (e.g., quercetin or YM155) can induce selective and complete cell death of undifferentiated hPSCs and, according to authors, is sufficient to prevent teratoma formation after transplantation of iPSC-derived cells. However, it is unlikely that any kind of preliminary clearance, even the most sophisticated pre-treatment, is able to secure the replanting iPSC or ESC, as after the selective removal of pluripotent cells, they re-emerge quickly by converting differentiated cells back into stem cells, which leads to the formation of tumors, This may be due to the disorder of let-7 regulation of its target Nr6a1 (also known as Germ cell nuclear factor - GCNF), an embryonic transcriptional repressor of pluripotency genes that regulates gene expression in adult fibroblasts following miRNA loss.
In this regard, it should be noted that teratoma formation by pluripotent stem cells may be caused by low activity of PTEN enzyme, reported to promote the survival of a small population (0,1-5% of total population) of highly tumorigenic, aggressive, teratoma-initiating embryonic-like carcinoma cells during differentiation. The survival of these teratoma-initiating cells is associated with failed repression of Nanog as well as a propensity for increased glucose and cholesterol metabolism. These teratoma-initiating cells also expressed a lower ratio of p53/p21 when compared to non-tumorigenic cells. In connection with the above safety problems, the use iPSC for cell therapy is still limited. However, they can be used for a variety of other purposes - including the modeling of disease, screening (selective selection) of drugs, toxicity testing of various drugs.
Interestingly, the tissue grown from iPSCs, placed in the "chimeric" embryos in the early stages of mouse development, practically do not cause an immune response (after the embryos have grown into adult mice) and are suitable for autologous transplantation At the same time, full reprogramming of adult cells in vivo within tissues by transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice results in teratomas emerging from multiple organs. See Figure in 
Chemically induced pluripotent cells (CiPSCs)
By using solely small molecules, Deng Hongkui and colleagues demonstrated that, endogenous “master genes” are enough for cell fate reprogramming. They induced a pluripotent state in adult cells from mice using seven small-molecule compounds. The effectiveness of the method is quite high: it was able to convert 0.2% of the adult tissue cells into iPSCs, which is comparable to the gene insertion conversion rate. The authors note that the mice generated from CiPSCs were "100% viable and apparently healthy for up to 6 months”.So. This chemical reprogramming strategy has potential use in generating functional desirable cell types for clinical applications.
Method for producing cells induced to differentiate from iPSCs in the teratoma under in vivo conditions
The fact that human iPSCs capable of forming teratomas not only in humans but also in some animal body, in particular in mice or pigs, allowed to develop a method for differentiation of iPSCs in vivo. For this purpose, iPSCs with an agent for inducing differentiation into target cells are injected to genetically modified pig or mouse that has suppressed immune system activation on human cells. The formed after a while teratoma is cut out and used for the isolation of the necessary differentiated human cells by means of monoclonal antibody to tissue specific markers on the surface of these cells. This method has been successfully used for the production of functional myeloid, erythroid and lymphoid human cells suitable for transplantation (yet only to mice). Mice engrafted with human iPSC teratoma-derived hematopoietic cells produced human B and T cells capable of functional immune responses. These results offer hope that in vivo generation of patient customized cells is feasible, providing materials that could be useful for transplantation, human antibody generation, and drug screening applications. Using MitoBloCK-6  and / or PluriSIn # 1 the differentiated progenitor cells can be further purified from teratoma forming pluripotent cells. The fact, that the differentiation takes place in a teratoma, offers hope that the resulting cells are sufficiently stable to stimuli able to cause their transition back to the dedifferentiated (pluripotent) state, and therefore safe. A similar in vivo differentiation system, yielding engraftable hematopoietic stem cells from mouse and human iPSCs in teratoma-bearing animals in combination with a maneuver to facilitate hematopoiesis, was described by Suzuki et al. They noted that neither leukemia nor tumors were observed in recipients after intravenous injection of iPSC-derived hematopoietic stem cells into irradiated recipients. Moreover, this injection resulted in multilineage and long-term reconstitution of the hematolymphopoietic system in serial transfers. Such system provides a useful tool for practical application of iPSCs in the treatment of hematologic and immunologic diseases.
Cell therapy with retina cells obtained from iPSCs
In the near future will start clinical trials designed to demonstrate the safety of the use of iPSCs for cell therapy of the people with age-related macular degeneration - a disease causing blindness through retina damaging. There are several articles describing methods for producing retinal cells from iPSCs  and how to use them for cell therapy. Reports of iPSC-derived retinal pigmented epithelium transplantation showed enhanced visual-guided behaviors of experimental animals for 6 weeks after transplantation. However, clinical trials have been successful: ten patients suffering from retinitis pigmentosa have had their eyesight restored—including a woman who had only 17 percent of her vision left. 
Generation of lung and airway epithelial cells from iPSC
Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden. So, there is an urgent need for effective cell therapy and lung tissue engineering. Several protocols have been developed for generation of the most cell types of the respiratory system, which may be useful for deriving patient-specific therapeutic cells.
Differentiation of iPSCs into reproductive cells
Some lines of iPSCs have the potentiality to differentiate into male germ cells and oocyte-like cells in an appropriate niche (by culturing in retinoic acid and porcine follicular fluid differentiation medium or seminiferous tubule transplantation). Moreover, iPSC transplantation make a contribution to repairing the testis of infertile mice, demonstrating the potentiality of gamete derivation from iPSCs in vivo and in vitro.
Induced progenitor stem cells
Methods of direct transdifferentiation
Due to the fact that the use of iPSC for cell therapy is associated with significant risk of cancer and tumors there is urgent need to develop methods for safer cell lines suitable for use in the clinic. An alternative to the methods of iPSC technique is the so-called "direct reprogramming" - induced by certain factors direct transdifferentiation of cells without passing through the stages of the pluripotent state,. The basis for this approach laid the study of Taylor and Jones, who showed that 5-azacytidine - reagent causing demethylation of DNA - can cause the formation of myogenic, chondrogenic, and adipogenic clones in the immortal cell line of mouse embryonic fibroblasts and Weintraub et al., who found that the activation of a single gene, later named MyoD1, is sufficient for such reprogramming,,. Compared with iPSC whose reprogramming need at least two weeks, the formation of induced progenitor cells occurs relatively quickly - sometimes within a few days and the efficiency of reprogramming are usually many times higher. This reprogramming does not always require cell division. But the main thing is that the resulting from such reprogramming multipotent somatic stem cells are more suitable for cell therapy because they do not form teratomas.
Forced transdifferentiation of mature cells by a single transcription factor
It was thought that only early embryonic cells could be coaxed into changing their identity. Mature cells are very resistant to changing their identity once they've committed to a specific kind. However, it has been found that brief expression of a single transcription factor, the ELT-7 GATA factor, can convert the identity of fully differentiated, highly specialized non-endodermal cells of the pharynx into fully differentiated intestinal cells in intact larvae and adult roundworm Caenorhabditis elegans. And there was no apparent requirement for a dedifferentiated intermediate during this transdifferentiation process.
Reprogramming by means of a phased process modeling regeneration
Another way of reprogramming is the simulation of the processes that occur during amphibian limb regeneration. In urodele amphibians, an early step in limb regeneration is skeletal muscle fiber dedifferentiation into a cellulate that proliferates to contribute new limb tissue, whereas, mammalian muscle cannot dedifferentiate after injury. However, sequential small molecule treatment of the muscle fiber with myoseverin, reversine (the aurora B kinase inhibitor) and some other chemicals: BIO (glycogen synthase-3 kinase inhibitor), lysophosphatidic acid (pleiotropic activator of G-protein-coupled receptors), SB203580 (p38 MAP kinase inhibitor), or SQ22536 (adenylyl cyclase inhibitor), causes the formation of new muscle cell types as well as other cell types such as precursors to fat, bone, and nervous system cells,.
Transdifferentiation by using an antibody
The researchers discovered GCSF-mimicking antibody that can activate a growth-stimulating receptor on marrow cells in a way that induces marrow stem cells—which normally develop into white blood cells—to become neural progenitor cells. The new technique, that enables researchers to search large libraries of antibodies and quickly select the ones with a desired biological effect, has been used for such purpose
Conditionally reprogrammed cells (CRCs)
Schlegel and Liu  demonstrated that the combination of feeder cells (a review is given in and) and a Rho kinase inhibitor (Y-27632)  induces normal and tumor epithelial cells from many tissues to proliferate indefinitely in vitro and this process occurs without the need for transduction of exogenous viral or cellular genes . These cells has been termed as "Conditionally Reprogrammed Cells (CRC)". The induction of CRCs is rapid and results from reprogramming of the entire cell population rather than the selection of a minor subpopulation. CRCs do not express high levels of proteins characteristic of iPSCs or embryonic stem cells (ESCs) (e.g., Sox2, Oct4, Nanog, or Klf4). This induction of CRCs is reversible, and removal of Y-27632 and feeders allows the cells to differentiate normally. CRC technology can generate 2×106 cells in 5 to 6 days from needle biopsies, and can generate cultures from cryopreserved tissue and from fewer than four viable cells. CRCs retain a normal karyotype and remain nontumorigenic. This technique also efficiently establishes cell cultures from human and rodent tumors. The ability to rapidly generate many tumor cells from small biopsy specimens and frozen tissue provides significant opportunities for cell-based diagnostics and therapeutics (including chemosensitivity testing) and greatly expands the value of biobanking. Using conditionally reprogrammed cells technology, researchers were able to identify an effective therapy for a patient with a rare type of lung tumor. In addition, the CRC method allows for the genetic manipulation of epithelial cells ex vivo and their subsequent evaluation in vivo in the same host. While their initial studies revealed that co-culturing of epithelial cells with Swiss 3T3 cells J2 was essential for the induction of CRCs, Schlegel and Liu  have now shown with transwell culture plates that physical contact between feeders and epithelial cells is not required for inducing CRCs and, more important, that irradiation of the feeder cells is required for this induction. Consistent with the transwell experiments, conditioned medium is shown to induce and maintain CRCs, which is accompanied by a concomitant increase of cellular telomerase activity. The activity of the conditioned medium correlated directly with radiation-induced apoptosis of the feeder cells. Thus, conditional reprogramming of epithelial cells is mediated by a combination of Y-27632 and a soluble factor(s) released by apoptotic feeder cells.
A different approach to obtain conditionally reprogrammed cells is to inhibit CD47 - a membrane protein which is the thrombospondin-1 receptor. It was shown that loss of CD47 permits sustained proliferation of primary murine endothelial cells, increases asymmetric division, and enables these cells to spontaneously reprogram to form multipotent embryoid body-like clusters. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells in vitro and in vivo. It is obvious that thrombospondin-1 is a key environmental signal that inhibits stem cell self-renewal via CD47. Thus, CD47 antagonists enable cell self-renewal and reprogramming by overcoming negative regulation of c-Myc and other stem cell transcription factors
Indirect lineage conversion (ILC)
A reprogramming methodology developed in which somatic cells transition through a plastic intermediate state of partially reprogrammed cells (pre-iPSC), induced by brief exposure to reprogramming factors, followed by differentiation by specially developed chemical environment (artificial niche). It is assumed that this new method could be both more efficient and safer, since it does not seem to produce tumors or other undesirable genetic changes, and results in much greater yield than other methods. However, the safety of these cells all the same questionable - considering that lineage conversion from pre-iPSC relies on the use of iPSC reprogramming conditions, it can not be excluded that a fraction of the cells could acquire pluripotent properties if they do not stop the de-differentation process in vitro or due to further de-differentiation in vivo.
Reprogramming induced by the influence on the outer membrane glycoprotein
A common feature of pluripotent stem cells, taken from different sources, is the specific nature of protein glycosylation of their outer membrane. That distinguishes them from most ( with the exception of white blood cells ) nonpluripotent cells. Obviously, changes in the glycosylation of outer membrane proteins are markers of the state of the cells connected in some way with pluripotency and differentiation. The "shift" in the nature of glycosylation, apparently, is not just the result of the initialization of some genes expression, but the mechanism performing the role of an important regulator of genes involved in the acquisition and maintenance of the undifferentiated state. For example, it is shown that activation of the glycoprotein ACA, linking glycosylphosphatidylinositol on the surface of the progenitor cells in human peripheral blood, induces increased expression of genes Wnt, Notch-1, BMI1 and HOXB4 through a signaling cascade PI3K/Akt/mTor/PTEN, and promotes the formation of self-renewing population of hematopoietic stem cells Furthermore, it is shown that dedifferentiation of progenitor cells induced by ACA- dependent signaling pathway leads to ACA- induced pluripotent stem cells, capable of differentiating in vitro into cells of all three germ layers. The study of lectins on their ability to maintain a culture of pluripotent human stem cells has led to the discovery of lectin Erythrina Cristagalli (ECA), capable of serving as a simple and highly effective matrix for the cultivation of human pluripotent stem cells.
Reprogramming through a physical approach
Cell adhesion protein E-cadherin is indispensable for a robust pluripotent phenotype. During reprogramming for iPS cell generation, N-cadherin can replace function of E-cadherin. These functions of cadherins obviously are not directly related to adhesion because, according to Guannan Su et al. sphere morphology helps maintaining the stemness of stem cells. Moreover, 3D sphere formation, due to forced growth of cells on low attachment surface, sometimes induces reprogramming. For example, neural progenitor cells can be generated from fibroblasts directly through a physical approach without introducing exogenous reprogramming factors.
Physical cues, in the form of parallel microgrooves on the surface of cell-adhesive substrates, can replace the effects of small-molecule epigenetic modifiers and significantly improve reprogramming efficiency. The mechanism relies on the mechanomodulation of the cells’ epigenetic state. Specifically,as the authors of this study believe: "decreased histone deacetylase activity and upregulation of the expression of WD repeat domain 5 (WDR5)—a subunit of H3 methyltranferase—by microgrooved surfaces lead to increased histone H3 acetylation and methylation". Nanofibrous scaffolds with aligned fibre orientation produce effects similar to those produced by microgrooves, suggesting that changes in cell morphology may be responsible for modulation of the epigenetic state.
Mouse embryonic stem cells (mESCs) undergo self-renewal in the presence of the cytokine, leukemia inhibitory factor (LIF). Following LIF withdrawal, mESCs differentiate, and this is accompanied by an increase in cell–substratum adhesion and cell spreading. Restricted cell spreading in the absence of LIF by either culturing mESCs on chemically defined, weakly adhesive biomaterial substrates, or by manipulating the cytoskeleton allowed to keep the cells in an undifferentiated and pluripotent state. The effect of restricted cell spreading on mESC self-renewal is not mediated by increased intercellular adhesion, as evidenced by the observations that inhibition of mESC adhesion using a function blocking anti E-cadherin antibody or siRNA do not promote differentiation.
Induced neural stem cells (iNSCs)
Stroke and many neurodegenerative disorders such as: Parkinson's disease, Alzheimer’s disease, amyotrophic lateral sclerosis need cell replacement therapy. The successful use of converted neural cells (cNs) in transplantations open a new avenue to treat such diseases. Nevertheless, induced neurons (iNs), directly converted from fibroblasts are terminally committed neurons that exhibit very limited proliferative ability and may not provide enough autologous donor cells for transplantation. The generation of self-renewing induced neural stem cells (iNSCs) provides additional advantages over iNs for both basic research and clinical applications. For example, under specific growth conditions, mouse fibroblasts can be reprogrammed with a single factor, Sox2, to form induced neural stem cells (iNSCs) that self-renew in culture and after transplantation can survive, integrate and do not form tumors in mouse brains. Induced neural stem cells can also be derived from adult human fibroblasts by non-viral techniques, thus offering a safe method to generate iNSCs for autologous transplantation or for the development of cell-based disease models. Methods of direct transformation of somatic cells into induced neural stem cells differ in their technique as shown in the review.
Some data provide proof of principle that it is possible, directly in the brain, to convert transplanted human fibroblasts and human astrocytes, which are engineered to express inducible forms of neural reprogramming genes, into neurons, when reprogramming genes (Ascl11, Brn2a, and Myt1l) are activated after transplantation using a drug in the animals’ drinking water. It was also shown that endogenous mouse astrocytes can be directly converted into neural nuclei (NeuN)-expressing neurons in situ.
Future studies will show which of these approaches proved to be most appropriate for clinic.
Oligodendrocyte precursor cells (OPCs)
Without myelin to insulate neurons, signals sent down nerve cell axons quickly lose power. Diseases that attack myelin, such as multiple sclerosis, result in nerve signals that are not efficient, because can not propagate to nerve endings, and as a consequence to cognitive, motor and sensory problems. Transplantation of oligodendrocyte precursor cells (OPCs), which can successfully create myelin sheaths around nerve cells, is a promising potential therapeutic strategy for diseases affecting myelin. However, there was no available source of engraftable OPCs. Therefore, direct lineage conversion of mouse and rat fibroblasts into oligodendroglial cells by forced expression of either eight or of the three transcription factors Sox10, Olig2 and Zfp536, laid the groundwork for therapies of a wide array of myelin disorders and spinal cord injury.
Induced cardiomyocytes (iCMs)
Development of regenerative therapeutic strategies to reverse the progression of advanced heart failure is one of the most urgent clinical needs of this century. Cell-based in vivo therapies may provide a transformative approach to augment vascular and muscle growth and to prevent non-contractile scar formation by delivering transcription factors or microRNAs to the heart. For example: Qian L. et al. & Srivastava D. demonstrate that cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of cardiac core transcription factors ( GATA4, MEF2C, TBX5 and for improved reprogramming plus ESRRG, MESP1, Myocardin and ZFPM2) after coronary ligation. These results implicated therapies that can directly remuscularize the heart without the need for cell transplantation. However, the efficiency of direct cardiac reprogramming in vivo by overexpression of cardiac core transcription factors in cardiac fibroblasts turned out to be very low and phenotype of received cardiomyocyte-like cells does not resemble those of a bona fide mature cardiomyocyte. Furthermore, transplantation of cardiac transcription factors into injured murine hearts resulted in poor cell survival and minimal expression of cardiac genes. So, further technical improvements are needed to make this technology more applicable in situ. Meanwhile, there have been some advances in the methods of obtaining cardiac myocytes in vitro. For example, Carpenter et al. demonstrated efficient cardiac differentiation of human iPS cells that gave rise to progenitors that were retained within the infarcted rat heart, and reduced remodeling of the heart after ischemic damage. Furthermore, in ischaemic cardiomyopathy, caused by the murine infarction model, targeted iPS cell transplantation synchronized failing ventricles, offering a regenerative strategy to achieve resynchronization and protection from decompensation by dint of improved left ventricular conduction and contractility, reduced scar, and reversal of structural remodelling. Palecek S P et al., have developed a protocol for generating almost pure populations of cardiomyocytes (up to 98% cardiomyocytes) from human pluripotent stem cells simply by modulating canonical Wnt signaling pathway at defined time points in the differentiation process, using readily accessible small molecule compounds. Discovery of the mechanisms controlling the formation of cardiomyocytes led to the development of the drug (ITD-1) which effectively clears the cell surface from TGF-β receptor type II and selectively inhibits the intracellular TGF-β signaling and thus selectively enhances the differentiation of uncommitted mesoderm to cardiomyocytes, but not to vascular smooth muscle and endothelial cells.
Lu et al. create heart constructs by repopulating decellularized mouse hearts with human induced pluripotent stem cell-derived multipotential cardiovascular progenitor cells. They found that the seeded multipotential cardiovascular progenitor cells migrate, proliferate and differentiate in situ into cardiomyocytes, smooth muscle cells and endothelial cells to reconstruct the decellularized hearts. In addition, they observed that heart's extracellular matrix of mouse (the substrate of heart scaffold) can send signals to guide the repopulated human multipotential cardiovascular progenitor cells into becoming the specialised cells needed for proper heart function. After 20 days of perfusion with growth factors, the engineered heart tissues started to beat again and were responsive to drugs.
Direct Reprogramming of Adult Cells to Nephron Progenitors (iNP)
Adult proximal tubule cells could be directly transcriptionally reprogrammed to nephron progenitors of the embryonic kidney, using a pool of six genes of instructive transcription factors (SIX1, SIX2, OSR1, Eyes absent homolog 1(EYA1), Homeobox A11 (HOXA11) and Snail homolog 2 (SNAI2)) that activated a network of genes consistent with a cap mesenchyme/nephron progenitor phenotype in the adult proximal tubule cell line. The generation of such cells may lead to cellular therapies for adult renal disease. Indeed, it has recently been shown that embryonic kidney organoids placed into adult rat kidney can undergo onward development and vascular development.
Bioengineering of the cells of blood vessels
Blood vessels build extensive networks that supply all cells with nutrients and oxygen throughout life. As blood vessels get older, they often become abnormal in structure and function, thereby contributing to numerous age-associated diseases including myocardial infarction, ischemic stroke and atherosclerosis of arteries supplying the heart, brain, and lower extremities. So, an important goal is to stimulate vascular growth for the collateral circulation to prevent the exacerbation of these diseases. A useful cell type for cell-based therapy designed to stimulate coronary collateral growth are Induced Vascular Progenitor Cells (iVPCs), generated by partially reprogramming endothelial cells. The vascular commitment of iVPCs is related to the epigenetic memory of endothelial cells, which engenders them as cellular components of growing blood vessels. That is why, when iVPCs were implanted into myocardium, they engrafted in blood vessels and increased coronary collateral flow better than iPSCs, mesenchymal stem cells, or native endothelial cells. An effective strategy to enhance stem cell function is ex vivo genetic modification. For example, genetic modification with Pim-1 kinase (a downstream effector of Akt, which positively regulates neovasculogenesis) of bone marrow–derived cells or human cardiac progenitor cells, isolated from failing myocardium results in durability of repair, together with the superior improvement of functional parameters of myocardial hemodynamic performance after cellular therapy of the injured myocardium with modified progenitor cells. Stem cells extracted from fat tissue after liposuction may be coaxed into progenitor smooth muscle cells (iPVSMCs) found in arteries and veins. In the future, iVPCs and iPVSMCs may become a necessary source for the creation of blood vessels networks for tissue engineering and reconstruction of organs for transplantation. For instance, it was found that the 2D culture system of human iPS cells in conjunction with the CD34 (a surface glycophosphoprotein expressed on developmentally early embryonic fibroblast), NP1 (receptor - neuropilin 1) and KDR (kinase insert domain-containing receptor) triple marker selection (for the isolation of vasculogenic precursor cells from human induced pluripotent stem cells) was capable to generate endothelial cells which after transplantation were able to form stable functional blood vessels in vivo, lasting for 280 d in mice.
In the treatment of infarction it is important to prevent the formation of fibrotic scar tissue. This can be achieved in vivo by means of transient application of paracrine factors changing the fate of the native heart progenitor stem cells from contributing to cardiac fibrotic scar tissue and towards cardiovascular tissue. For example, it was shown in a mouse myocardial infarction model, that a single intramyocardial injection of human vascular endothelial growth factor-A mRNA (VEGF-A modRNA), synthetically modified so that it escapes the normal defense system of the body, results in long-term improvement of heart function due to mobilization of epicardial progenitor cells and redirection of their differentiation toward cardiovascular cell types 
Bioengineering of blood stem cells
Definitive hematopoiesis emerges during embryogenesis via an endothelial-to-hematopoietic transition. Fairly simple combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6, is sufficient to induce in vitro this complex, dynamic, and multistep developmental program leading to the formation of endothelial-like precursor cells, with the subsequent appearance of hematopoietic cells.
Red blood cells (RBC)
Red blood cells (RBC) transfusion is necessary for many patients with emergency or hematological disorders. However, to date the supply of RBCs remains labile and dependent on voluntary donations. In addition, the transmission of infectious disease via blood transfusion from unspecified donors remains a risk. Establishing a large quantity of safe RBCs would help to address this issue. New technologies for ex vivo erythroid cell generation will hopefully provide alternative transfusion products to meet present and future clinical requirements. In favor of this suggest data that RBCs generated in vitro from mobilized CD34 positive cells have normal survival when transfused into an autologous recipient. Unfortunately, the RBC produced in vitro contained exclusively fetal hemoglobin (HbF) which rescues the functionality of these RBCs. However, in vivo the switch of fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from induced pluripotent stem cells was observed. But then there is another problem: although RBCs do not have nuclei, and therefore can not form a tumor, their immediate precursors the erythroblasts do. The terminal maturation of erythroblasts into functional RBCs requires a complex remodeling process which ends with extrusion of the nucleus and the formation of an enucleated RBC. Alas, cell reprogramming methodologies at present often disrupt these processes of enucleation and therefore transfusion of in vitro generated RBCs or their immediate precursors the erythroblasts still insufficiently protected against the possibility of tumors formation. However, recently Bouhassira and colleagues found that exposing CD34 positive cells to a short pulse of cytokines favorable for erythroid differentiation prior to stem cell expansion followed by progenitor expansion produced on the order more yield of erythroid cells than the yields observed previously. And the most important: these red blood cells expressed a globin profile similar to that of the developmental age of the CD34 positive cells It is also interesting to note that an important role in normal blood cell development plays the aryl hydrocarbon receptor (AhR) pathway (which has been shown to be involved in the promotion of cancer cell development). AhR activation in human hematopoietic progenitor cells (HPs) drives an unprecedented expansion of HPs, megakaryocyte- and erythroid-lineage cells.
See also: Migliaccio AR, Whitsett C, Papayannopoulou T, Sadelain M. (2012) The potential of stem cells as an in vitro source of red blood cells for transfusion. Review. Cell Stem Cell.;10(2):115-9
Platelets play an important role in preventing hemorrhage in thrombocytopenic patients and patients with thrombocythemia. A significant problem for multitransfused patients is refractoriness to platelet transfusions. Thus, the ability to generate platelet products ex vivo and, notably, platelet products lacking HLA antigens in serum free media, would have great clinical value. Some success in this direction has achieved Figueiredo et al. Using an RNA interference-based mechanism in which a lentiviral vector was used to express short-hairpin RNAi targeting β2-microglobulin transcripts in CD34 positive cells, they generated platelets demonstrating an 85% reduction in class I HLA antigens. These platelets appeared to have normal function in vitro
A specialised type of white blood cell, known as cytotoxic T lymphocytes (CTLs), are produced by the immune system and are able to recognise specific markers on the surface of various infectious or tumour cells, causing them to launch an attack to kill the harmful cells. Thence immunotherapy with functional antigen-specific T cells is potentially an effective therapeutic strategy for combating many types of cancer and viral infection. Unfortunately, sources of such cells for therapeutic purposes are limited, because they are produced in small numbers naturally and have a short lifespan. A potentially efficient approach for generating antigen-specific CTLs is to revert mature immune T cells into iPSCs, which possess indefinite proliferative capacity in vitro, and after their multiplication to coaxed them to redifferentiate back into T cells Even more opportunities promises a method that combine iPSC and chimeric antigen receptor (CAR)  technologies to generate human T cells targeted to CD19, an antigen expressed by malignant B cells, in tissue culture. This approach of generating therapeutic human T cells 'in the dish' may be useful for cancer immunotherapy and other medical applications because such 'living drugs' have fewer side effects, once injected - stay in the body and move around to stop recurrences.
Invariant natural killer T (iNKT) cells has great clinical potential as adjuvant for cancer immunotherapy. iNKT cells act as innate T lymphocytes and serve as a bridge between the innate and acquired immune systems. They augment anti-tumor responses by producing interferon-gamma (IFN-γ). A conceptual method is proposed for the use of iPSC-derived iNKT cells for adjuvant cell therapy against cancer, which is composed of four segments: (1) collection of iNKT cells, (2) reprogramming of iNKT cells into iPSCs, (3) re-differentiation of iNKT cell-derived iPSCs into iNKT cells and their expansion in vitro, and (4) injection of iPSC-derived iNKT cells into tumor-bearing animals.
Dendritic cells (DC) are specialized to control T-cell responses. DC with appropriate genetic modifications may survive long enough to stimulate antigen-specific CTL and, after that, be completely eliminated. It was shown that DC-like antigen-presenting cells obtained from human induced pluripotent stem cells may serve as an unlimited source for vaccination therapy.
Induced Mesenchymal stem cells (iMSCs)
Induction of human iPSc to Generate Mesenchymal Stem/Stromal Cells
Because of their immunosuppressive properties and ability to differentiate into a wide range of mesenchymal-lineage tissues, mesenchymal stem/stromal cells (MSCs) are under intense investigation for applications in cardiac, renal, neural, joint, and bone repair, as well as in inflammatory conditions and hemopoietic cotransplantation. MSCs are typically harvested from adult bone marrow or fat, but these not only require painful invasive procedures but are low-frequency sources, with MSCs making up only 0.001%– 0.01% of bone marrow cells and 0.05% in liposuction aspirates. Of concern for autologous use, particularly in the elderly most in need of tissue repair, MSCs decline in quantity and quality with age. However, induced pluripotent stem cells (iPSCs) could be obtained by the cells rejuvenation of even centenarian human. Because iPSCs can be harvested free of ethical constraints and culture can be expanded indefinitely, they are an advantageous source of MSCs. Chen and colleagues discovered that iPSCs treatment with SB-431542 (that inhibits the activin/TGF- pathways by blocking phosphorylation of ALK4, ALK5, and ALK7 receptors) leads to rapid and uniform MSC generation from human iPSCs. These iPS-MSCs possibly lack teratoma-forming ability, display a normal stable karyotype in culture, and exhibit growth and differentiation characteristics that closely resemble those of primary MSCs described, has considerable potential for the in vitro scale-up required to enable a wide range of MSC-based therapies. Unfortunately, currently there is no data on the in vivo efficacy and long-term safety of iPSC-derived MSCs generated by this method.
It is interesting to note that besides cell therapy in vivo the culture of human mesenchymal stem cells can be used in vitro for mass production of exosomes, which, as it turned out, are ideal vehicles for drug delivery.
Dedifferentiated adipocytes: an alternative source of MSC
Adipose tissue, because of its abundance and relatively less invasive harvest methods, represents a practical and appealing source of mesenchymal stem cells (MSCs). Unfortunately, there are only 0.05% MSCs in liposuction aspirates. However, a large amount of mature adipocytes, which generally lost their proliferative abilities, and therefore often discarded, can be easily isolated from the adipose cell suspension and dedifferentiated into lipid-free fibroblast-like cells, named dedifferentiated fat (DFAT) cells. DFAT cells re-establish active proliferation ability and undertake multipotent capacities. Compared with adult stem cells, DFAT cells showed unique advantages in their abundance, isolation and homogeneity. Under proper induction culture in vitro or environment in vivo, DFAT cells could demonstrate adipogenic, osteogenic, chondrogenic and myogenic potentials. They also could exhibit perivascular characteristics and elicit neovascularization.
Induced chondrogenic cells (iChon cells)
Cartilage is the connective tissue responsible for frictionless joint movement. Its degeneration ultimately results in complete loss of joint function in the late stages of osteoarthritis. As an avascular and hypocellular tissue, cartilage has a very limited capacity for self-repair. Chondrocytes are the only cell type in cartilage, in which they are surrounded by the extracellular matrix that they secrete and assemble. One conceivable method of producing cartilage is to induce it from iPS cells. Alternatively, it is possible to convert fibroblasts directly into induced chondrogenic cells (iChon cells) without an intermediate iPS cell stage, by inserting three reprogramming factors (c-MYC, KLF4, and SOX9). The human iChon cells expressed marker genes for chondrocytes (type II collagen) but not fibroblasts. Implanted into defects created in the articular cartilage of rats’, the human iChon cells were able to survive and form cartilaginous tissue for at least four weeks, but not tumors. Nevertheless, the method used in the study makes use of c-MYC, which is thought to have a major role in tumorigenesis, and employs a retrovirus to introduce the reprogramming factors. So, it could not be applied without modification in human therapy.
Sources of cells for reprogramming
The most frequently used source for reprogramming are blood cells. and fibroblasts, obtained by biopsy of the skin, but more convenient to receive the body cells from the urine. This method does not require a biopsy or blood sampling and therefore harmless to the patient. Urine-derived stem cells have capacity for multipotent differentiation. They are able to differentiate into endothelial, osteogenic, chondrogenic, adipogenic, skeletal myogenic and neurogenic lineages, but did not form teratomas. Therefore, their epigenetic memory better suited to the reprogramming into iPS cells. However, there are very few cells in the urine, the efficiency of turning them into induced stem cells is low, whereas the risk of bacterial contamination higher than with other sources of cells.
Another promising source of cells for reprogramming are mesenchymal stem cells derived from human hair follicles.
It is important to note that the origin of somatic cells used for reprogramming may influence the efficiency of reprogramming, the functional properties of the resulting induced stem cells and the ability to form tumors.
While selecting the source for reprogramming, into account should be taken the fact that iPSCs retain an epigenetic memory of their tissue of origin, and that this impacts their differentiation potential This epigenetic memory does not necessarily manifest itself at the pluripotency stage – iPSCs derived from different tissues exhibit proper morphology, express pluripotency markers, and are able to differentiate into the three embryonic layers in vitro and in vivo. However, this epigenetic memory may manifest later, during re-differentiation into specific cell types that require the specific loci that have residual epigenetic marks.
References for further reading
- Shinya Yamanaka (2012) Induced Pluripotent Stem Cells: Past, Present, and Future. Cell Stem Cell, 10(6), 678-684, 10.1016/j.stem.2012.05.005
- Kazutoshi Takahashi and Shinya Yamanaka (2013) Induced pluripotent stem cells in medicine and biology. Development, 140, 2457-2461. doi:10.1242/dev.092551
- Grace E. Asuelime and Yanhong Shi (2012) A case of cellular alchemy: lineage reprogramming and its potential in regenerative medicine J Mol Cell Biol doi: 10.1093/jmcb/mjs005
- Lensch, M. W., & Mummery, C. L. (2013) From Stealing Fire to Cellular Reprogramming: A Scientific History Leading to the 2012 Nobel Prize. Stem Cell Reports, 1(1), 5-17 doi:10.1016/j.stemcr.2013.05.001
- Special Issue (October 2013) Induced Pluripotent Stem Cells. Genomics, Proteomics & Bioinformatics. 11(5), 257-334
- Ji Lin, Mei-rong Li, Dong-dong Ti, et al. & Wei-dong Han (2013) Microenvironment-evoked cell lineage conversion: Shifting the focus from internal reprogramming to external forcing Review Article. Ageing Research Reviews
- Takahashi K. (2012) Cellular reprogramming – lowering gravity on Waddington's epigenetic landscape. J Cell Sci.; 125 (11), 2553-2560. doi: 10.1242/jcs.084822
- Nobel Prize in Physiology or Medicine 2012 Awarded for Discovery That Mature Cells Can Be Reprogrammed to Become Pluripotent
- Samer MI Hussein, Andras A Nagy (2012) Progress made in the reprogramming field: new factors, new strategies and a new outlook. Current Opinion in Genetics & Development. 22(5), 435–443 http://dx.doi.org/10.1016/j.gde.2012.08.007
- Yemin Zhang, Lin Yao, Xiya Yu, Jun Ou, Ning Hui and Shanrong Liu (2012) A poor imitation of a natural process: A call to reconsider the iPSC engineering technique. Cell Cycle, 11(24), 4536 - 4544
- Ignacio Sancho-Martinez, Sung Hee Baek & Juan Carlos Izpisua Belmonte (2012) Lineage conversion methodologies meet the reprogramming toolbox. Nature Cell Biology, 14, 892–899 doi:10.1038/ncb2567
- Mochiduki, Y. and Okita, K. (2012) Methods for iPS cell generation for basic research and clinical applications. Biotechnology Journal, 7: 789–797. doi: 10.1002/biot.201100356
- Rosalinda Madonna (2012) Human-Induced Pluripotent Stem Cells: In Quest of Clinical Applications Molecular Biotechnology, 52(2), 193-203 DOI: 10.1007/s12033-012-9504-0
- M. Lorenzo, A. Fleischer, D. Bachiller (2012) Generation of Mouse and Human Induced Pluripotent Stem Cells (iPSC) from Primary Somatic Cells. Stem Cell Reviews and Reports DOI 10.1007/s12015-012-9412-5 (detailed protocols & all-encompassing instructions)
- Detailed protocols for reprogramming and for analysis of iPSCs
- Buganim, Y., Faddah, D. A., & Jaenisch, R. (2013) Mechanisms and models of somatic cell reprogramming. Nature Reviews Genetics, 14(6), 427-439. doi: 10.1038/nrg3473 researchgate.net [PDF]
- Yamanaka S, Blau HM. (2010) Nuclear reprogramming to a pluripotent state by three approaches. Nature. , 465 (7299) :704-712.
- Gurdon J. B. and Ian Wilmut (2011) Nuclear Transfer to Eggs and Oocytes Cold Spring Harb Perspect Biol; 3: a002659
- Masahito Tachibana, Paula Amato, Michelle Sparman, et al. & Shoukhrat Mitalipov (2013) Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer. Cell, 153(6), 1228-1238 http://dx.doi.org/10.1016/j.cell.2013.05.006
- Scott Noggle et al. & Dieter Egli (2011) Human oocytes reprogram somatic cells to a pluripotent state Nature 478 (7367), 70-75 doi: 10.1038/nature10397
- Pan, G., Wang, T., Yao, H. and Pei, D. (2012), Somatic cell reprogramming for regenerative medicine: SCNT vs. iPS cells. Bioessays, 34: 472–476. doi: 10.1002/bies.201100174
- Do JT, et al. (2007) Erasure of cellular memory by fusion with pluripotent cells. Stem Cells 25:1013-1020
- Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell; 131 (5):861-872.
- Wei Wang, et al. and Pentao Liu (2011) Rapid and efficient reprogramming of somatic cells to induced pluripotent stem cells by retinoic acid receptor gamma and liver receptor homolog 1. PNAS 2011; published ahead of print October 11, 2011, doi: 10.1073/pnas.1100893108
- Laure Lapasset et al. and Jean-Marc Lemaitre (2011) Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state Genes Dev. 25: 2248-2253; doi: 10.1101/gad.173922.111
- Hongyan Zhou, Shili Wu, Jin Young Joo, et al & Sheng Ding (2009) Generation of Induced Pluripotent Stem Cells Using Recombinant Proteins . Cell Stem Cell; 4 (5), 381-384. doi: 10.1016/j.stem.2009.04.005
- Li, Z. and Rana, T. M. (2012) Using MicroRNAs to Enhance the Generation of Induced Pluripotent Stem Cells. Current Protocols in Stem Cell Biology. 20:4 D.4.1-4D.4.14. DOI: 10.1002/9780470151808.sc04a04s20
- Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE. (2011) Highly Efficient miRNA-Mediated Reprogramming of Mouse and Human Somatic Cells to Pluripotency. Cell Stem Cell; 8 (4):376-88
- Norikatsu Miyoshi, et al. & Masaki Mori (2011) Reprogramming of Mouse and Human Cells to Pluripotency Using Mature MicroRNAs. Cell Stem Cell. 8 (6), 633-638.
- Jayawardena T M., Egemnazarov B, Finch E A, et al, & Dzau V J. (2012) MicroRNA-Mediated In Vitro and In Vivo Direct Reprogramming of Cardiac Fibroblasts to Cardiomyocytes doi: 10.1161/CIRCRESAHA.112.269035
- Xichen Bao, Xihua Zhu, Baojian Liao, et al & Miguel A Esteban (2013) MicroRNAs in somatic cell reprogramming. Current Opinion in Cell Biology, 25(2), 208–214 http://dx.doi.org/10.1016/j.ceb.2012.12.004
- Naohisa Yoshioka, Edwige Gros, Hai-Ri Li, et al. & Steven F. Dowdy (2013) Efficient Generation of Human iPSCs by a Synthetic Self-Replicative RNA. Cell Stem Cell, 13(2), 246-254, doi: 10.1016/j.stem.2013.06.001
- Pingping Hou, Yanqin Li, Xu Zhang, et al. and Hongkui Deng (2013) Pluripotent Stem Cells Induced from Mouse Somatic Cells by Small-Molecule Compounds. Science Express 1239278 DOI: 10.1126/science.1239278
- Jem A. Efe and Sheng Ding (2011) The evolving biology of small molecules: controlling cell fate and identity Phil. Trans. R. Soc. B August 12, 2011 366:2208-2221; doi: 10.1098/rstb.2011.0006
- Stadtfeld M, Apostolou E, Ferrari F et al. & Hochedlinger K.(2012) Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells. Nat Genet. 44(4):398-405, S1-2. doi: 10.1038/ng.1110
- Pandian, G. N. and Sugiyama, H. (2012) Programmable genetic switches to control transcriptional machinery of pluripotency. Biotechnology Journal, 7(6): 798–809. doi: 10.1002/biot.201100361
- Pandian GN, Nakano Y, Sato S, Morinaga H, Bando T, Nagase H, Sugiyama H. (2012) A synthetic small molecule for rapid induction of multiple pluripotency genes in mouse embryonic fibroblasts. Sci Rep. ;2:544. doi: 10.1038/srep00544
- Slack JM. (2009) Metaplasia and somatic cell reprogramming. J Pathol.; 217 (2): 161-168. doi: 10.1002/path.2442
- Wei, G., Schubiger, G., Harder, F. and Müller, A. M. (2000), Stem Cell Plasticity in Mammals and Transdetermination in Drosophila: Common Themes?. STEM CELLS, 18: 409-414. doi: 10.1634/stemcells.18-6-409
- Melanie I. Worley, Linda Setiawan, and Iswar K. Hariharan (2012) Regeneration and Transdetermination in Drosophila Imaginal Discs. Annual Review of Genetics. 46: 289-310 DOI: 10.1146/annurev-genet-110711-155637
- Stange DE, Koo BK, Huch M, et al. & Clevers H.( 2013) Differentiated Troy chief cells act as 'reserve' stem cells to generate all lineages of the stomach epithelium. Cell, 155 (2), 357-368, doi:10.1016/j.cell.2013.09.008
- Tata, P. R., Mou, H., Pardo-Saganta, A., et al. & Rajagopal, J. (2013). Dedifferentiation of committed epithelial cells into stem cells in vivo. Nature. 503(7475), 218–223 doi:10.1038/nature12777
- Kusaba, T., Lalli, M., Kramann, R., Kobayashi, A., & Humphreys, B. D. (2013) Differentiated kidney epithelial cells repair injured proximal tubule. PNAS, 201310653. doi:10.1073/pnas.1310653110
- Michael H. Sieweke, Judith E. Allen (2013) Beyond Stem Cells: Self-Renewal of Differentiated Macrophages. Science : 342(6161) DOI: 10.1126/science.1242974
- Sandoval-Guzmán, T., Wang, H., Khattak, S., et al & Simon, A. (2013). Fundamental Differences in Dedifferentiation and Stem Cell Recruitment during Skeletal Muscle Regeneration in Two Salamander Species. Cell Stem Cell. http://dx.doi.org/10.1016/j.stem.2013.11.007
- Kuroda, Y., Kitada, M., Wakao, S., et al. & Dezawa, M. (2010) Unique multipotent cells in adult human mesenchymal cell populations. PNAS , 107(19), 8639-8643. doi:10.1073/pnas.0911647107
- Kuroda, Y., Wakao, S., Kitada, M., et al. & Dezawa, M. (2013). Isolation, culture and evaluation of multilineage-differentiating stress-enduring (Muse) cells. Nature Protocols, 8(7), 1391-1415.doi:10.1038/nprot.2013.076
- Heneidi S, Simerman AA, Keller E, Singh P, Li X, et al. (2013) Awakened by Cellular Stress: Isolation and Characterization of a Novel Population of Pluripotent Stem Cells Derived from Human Adipose Tissue. PLoS ONE 8(6): e64752. doi:10.1371/journal.pone.0064752
- Shigemoto T, Kuroda Y, Wakao S, Dezawa M (2013) A Novel Approach to Collecting Satellite Cells From Adult Skeletal Muscles on the Basis of Their Stress Tolerance Stem Cells Trans Med 2 (7) 488-498 doi:10.5966/sctm.2012-0130
- Sisakhtnezhad, S., & Matin, M. M. (2012). Transdifferentiation: a cell and molecular reprogramming process. Cell and Tissue Research, 348(3), 379-396. DOI: 10.1007/s00441-012-1403-y
- Andras Dinnyes, Xiuchun Cindy Tian, and Bj¨orn Oback (2013) Nuclear Transfer for Cloning Animals. In: Stem Cells. Ed. by Robert A. Meyers. Wiley-Blackwell ISBN 978-3-527-32925-0, pp. 299 - 344
- Jerome Jullien, Vincent Pasque, Richard P. Halley-Stott, Kei Miyamoto & J. B. Gurdon (2011) Mechanisms of nuclear reprogramming by eggs and oocytes: a deterministic process? Nature Reviews Molecular Cell Biology 12, 453-459 doi: 10.1038/nrm3140
- Keith HS Campbell (2002) A background to nuclear transfer and its applications in agriculture and human therapeutic medicine. J Anat.; 200 (3): 267-275. doi: 10.1046/j.1469-7580.2002.00035.x
- S. Morteza Hosseini, Mehdi Hajian, Mohsen Forouzanfar et al. and Mohammad H. Nasr-Esfahani (2012) Enucleated Ovine Oocyte Supports Human Somatic Cells Reprogramming Back to the Embryonic Stage. Cellular Reprogramming, 14 (2): 155-163. doi: 10.1089/cell.2011.0061
- Hui Yang, Linyu Shi, Bang-An Wang, et al. & Jinsong Li. (2012) Generation of Genetically Modified Mice by Oocyte Injection of Androgenetic Haploid Embryonic Stem Cells. Cell; 149 (3), 605-617 DOI: 10.1016/j.cell.2012.04.002
- Hayashi K, et al., & Saitou M. (2012) Offspring from Oocytes Derived from in Vitro Primordial Germ Cell–Like Cells in Mice. Science DOI: 10.1126/science.1226889
- Satoshi Kishigami, Eiji Mizutani, Hiroshi Ohta, et al. & Teruhiko Wakayama (2006) Significant improvement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer. Biochemical and Biophysical Research Communications 340(1), 183–189 http://dx.doi.org/10.1016/j.bbrc.2005.11.164
- Sayaka Wakayama, Takashi Kohda, Haruko Obokata et al. and Teruhiko Wakayama (2013) Successful serial cloning in the mouse over multiple generations. Cell Stem Cell, 12(3), 293–297 DOI: 10.1016/j.stem.2013.01.005
- Tachibana et al., ang S. Mitalipov (2013) Human embryonic stem cells derived by somatic nuclear transfer, Cell, doi.org/10.1016/j.cell.2013.05.006
- Masahito Tachibana, Michelle Sparman, and Shoukhrat Mitalipov (2010) Chromosome transfer in mature oocytes. Nat Protoc. 2010; 5(6): 1138–1147. doi: 10.1038/nprot.2010.75
- Daniel Paull, Valentina Emmanuele, Keren A. Weiss et al. & Dieter Egli. (2012) Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants. Nature, DOI: doi:10.1038/nature11800
- Tachibana, M., Amato, P., Sparman, M., et al. & Mitalipov, S. (2012). Towards germline gene therapy of inherited mitochondrial diseases Nature DOI: 10.1038/nature11647
- Principles of Cloning (Second Edition). Edited by Jose Cibelli et al, Academic Press, 2014 Elsevier Inc. ISBN 978-0-12-386541-0
- Stevens LC. (1970) The development of transplantable teratocarcinomas from intratesticular grafts of pre-and postimplantation mouse embryos. Dev Biol.; 21 (3) :364-382
- Mintz B, Cronmiller C, Custer RP. (1978) Somatic cell origin of teratocarcinomas. Proc Natl Acad Sci U S A; 75 (6) :2834-2838
- Mintz B, Illmensee K. (1975) Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci U S A; 72 (9) :3585-3589
- MARTIN, G. R. & EVANS, M. J. (1975). Differentiation of clonal lines of teratocarcinoma cells: formation of embryoid bodies in vitro. Proc. Natn. Acad. Sci. U.S.A. 72, 1441-1445
- Illmensee, K. & Mintz, B. (1976) Totipotency and normal differentiation of single teratocarcinoma cells cloned by injection into blastocysts. Proc. Natl Acad. Sci. USA 73, 549–553
- Martin, GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad. Sci. USA 78, 7634-7638
- Martin CR (1980) Teratocarcinomas and mammalian embriogenesis. Science, 209, 768-776
- Papaioannou VE, Gardner RL, Mc Burney MV, Babinet C., Evans MJ, (1978) Participation of cultured teratocarcinoma cells in mouse embriogenesis. J. Embriol.Exp. Morphol., 44, 93-104
- GRAHAM, C. F. (1977). Teratocarcinoma cells and normal mouse embryogenesis. In Concepts in Mammalian Embryogenesis (ed. M. I. Sherman), pp. 315-394. Cambridge: M.I.T. Press
- ILLMENSEE, K. (1978). Reversion of malignancy and normalized differentiation of teratocarcinoma cells in chimeric mice. In Genetic Mosaics and Chimeras in Mammals (ed. L. Russell), pp. 3-24. New York: Plenum
- Boland, M. J. et al. (2009) Adult mice generated from induced pluripotent stem cells.Nature 461, 91–94.
- Kang, L., Wang, J., Zhang, Y., Kou, Z. & Gao, S. iPS cells can support full-term development of tetraploid blastocyst-complemented embryos. Cell Stem Cell 5, 135–138 (2009)
- Yehezkel S, Rebibo-Sabbah A, Segev Y, Tzukerman M, Shaked R, Huber I, Gepstein L, Skorecki K, Selig S (2011) Reprogramming of telomeric regions during the generation of human induced pluripotent stem cells and subsequent differentiation into fibroblast-like derivatives. Epigenetics. Jan 1 2011, 6 (1) :63-75
- West MD, Vaziri H. (2010) Back to immortality: the restoration of embryonic telomere length during induced pluripotency. Regen Med.; 5 (4) :485-488
- Marión RM, Blasco MA. (2010) Telomere rejuvenation during nuclear reprogramming. Curr Opin Genet Dev. 2010 Apr; 20 (2) :190-196
- Gourronc FA, Klingelhutz AJ. (2011) Therapeutic opportunities: Telomere maintenance in inducible pluripotent stem cells. Mutat Res.
- Tongbiao Zhao, Zhen-Ning Zhang, Zhili Rong & Yang Xu (2011) Immunogenicity of induced pluripotent stem cells Nature 474, 212-215 doi: 10.1038/nature10135
- Dhodapkar MV, Dhodapkar KM. (2011) Spontaneous and therapy-induced immunity to pluripotency genes in humans: clinical implications, opportunities and challenges. Cancer Immunol Immunother.; 60 (3) :413-418
- Ivan Gutierrez-Aranda (2010) Human Induced Pluripotent Stem Cells Develop Teratoma More Efficiently and Faster than Human Embryonic Stem Cells Regardless of the Site of Injection. Stem Cells; 28:1568-1570
- Chan-Jung Chang, Koyel Mitra, Mariko Koya et al. & Eric E. Bouhassira (2011) Production of Embryonic and Fetal-Like Red Blood Cells from Human Induced Pluripotent Stem Cells. PLoS One.; 6 (10): e25761. doi: 10.1371/journal.pone.0025761
- Deepa V. Dabir, Samuel A. Hasson, Kiyoko Setoguchi, et al & Carla M. Koehler (2013) A Small Molecule Inhibitor of Redox-Regulated Protein Translocation into Mitochondria. 25(1), 81–92 http://dx.doi.org/10.1016/j.devcel.2013.03.006
- Uri Ben-David, Qing-Fen Gan, Tamar Golan-Lev, et al & Nissim Benvenisty (2013)Selective Elimination of Human Pluripotent Stem Cells by an Oleate Synthesis Inhibitor Discovered in a High-Throughput Screen Cell Stem Cell, 12(2), 167-179 http://dx.doi.org/10.1016/j.stem.2012.11.015
- Lou, K. J. (2013). Small molecules vs. teratomas. SciBX: Science-Business eXchange, 6(7). doi:10.1038/scibx.2013.158
- Lee, M. O., Moon, S. H., Jeong, H. C. et al. and Cha, H. J. (2013). Inhibition of pluripotent stem cell-derived teratoma formation by small molecules. PNAS,110(35), E3281-E3290 doi:10.1073/pnas.1303669110
- Chad Tang, Irving L. Weissman, and Micha Drukker (2012) The Safety of Embryonic Stem Cell Therapy Relies on Teratoma Removal. Oncotarget; 3 (1): 7-8
- Chaffer, CL, Brueckmann, I., Scheel, C., Kaestli, AJ, Wiggins, PA, Rodrigues, LO, Brooks, M., Reinhardt, F., Su, Y., Polyak, K., et al. (2011) Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc. Natl. Acad. Sci. 108, 7950-7955
- Piyush B. Gupta, Christine M. Fillmore, Guozhi Jiang, Sagi D. Shapira, Kai Tao, Charlotte Kuperwasser, Eric S. Lander (2011) Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells. Cell, 146 (4), 633-644
- Fu W, Wang SJ, Zhou GD et al. and Zhang WJ. (2012) Residual undifferentiated cells during differentiation of induced pluripotent stem cells in vitro and in vivo. Stem Cells and Development, 21 (4): 521-529. doi: 10.1089/scd.2011.0131
- Allan M. Gurtan, Arvind Ravi, Peter B. Rahl, et al. and Phillip A. Sharp (2013) Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts. Genes & Dev. 27(12): 941-954 doi:10.1101/gad.215376.113
- Hongran Wang , Xiaohong Wang, Xueping Xu, Thomas P. Zwaka, Austin J. Cooney (2013) Epigenetic Re-programming of the Germ Cell Nuclear Factor Gene is Required for Proper Differentiation of Induced Pluripotent Cells. DOI: 10.1002/stem.1367
- Lindgren AG, Natsuhara K, Tian E, Vincent JJ, Li X, et al. (2011) Loss of Pten Causes Tumor Initiation Following Differentiation of Murine Pluripotent Stem Cells Due to Failed Repression of Nanog. PLoS ONE 6(1): e16478. doi:10.1371/journal.pone.0016478
- Grad, I., Hibaoui, Y., Jaconi,. et al. & Feki, A. (2011) NANOG priming before full reprogramming may generate germ cell tumours. Eur. Cell Mater, 22, 258-274
- Hideyuki Okano, Masaya Nakamura, Kenji Yoshida, et al & Kyoko Miura (2013) Steps Toward Safe Cell Therapy Using Induced Pluripotent Stem Cells. Circulation Research.; 112: 523-533 doi: 10.1161/CIRCRESAHA.111.256149
- Justine J Cunningham, Thomas M Ulbright, Martin F Pera & Leendert H J Looijenga (2012) Lessons from human teratomas to guide development of safe stem cell therapies. Nature Biotechnology, 30, 849–857 doi:10.1038/nbt.2329
- Bellin, M., Marchetto, M. C., Gage, F. H., & Mummery, C. L. (2012) Induced pluripotent stem cells: the new patient?. Nature Reviews Molecular Cell Biology. 13, 713-726 doi:10.1038/nrm3448
- Sandoe, J., & Eggan, K. (2013) Opportunities and challenges of pluripotent stem cell neurodegenerative disease models. Nature neuroscience, 16(7), 780-789. doi:10.1038/nn.3425
- Kazutoshi Takahashi and Shinya Yamanaka (2013) Induced pluripotent stem cells in medicine and biology. Development, 140, 2457-2461. doi:10.1242/dev.092551
- Xuemei Fu, Yang Xu (2012) Challenges to the clinical application of pluripotent stem cells: towards genomic and functional stability. Genome Medicine 2012, 4:55 (28 June 2012).
- Ryoko Araki, Masahiro Uda, Yuko Hoki, et al. & Masumi Abe (2013) Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature, (2013) doi:10.1038/nature11807
- Monya Baker (2013) Safety of induced stem cells gets a boost. Fears of immune response have been overestimated. Nature 493, 145 doi:10.1038/493145a
- M. Wahlestedt, G. L. Norddahl, G. Sten, A. Ugale, M.-A. Micha Frisk, R. Mattsson, T. Deierborg, M. Sigvardsson, D. Bryder. An epigenetic component of hematopoietic stem cell aging amenable to reprogramming into a young state. Blood, 2013; DOI: 10.1182/blood-2012-11-469080
- María Abad, Lluc Mosteiro, Cristina Pantoja, et al. & Manuel Serrano (2013) Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature, doi:10.1038/nature12586
- De Los Angeles, A., & Daley, G. Q. (2013) A chemical logic for reprogramming to pluripotency doi: 10.1038/cr.2013.119
- Federation, A. J., Bradner, J. E., & Meissner, A. (2013) The use of small molecules in somatic-cell reprogramming. Trends in cell biology. Doi: 10.1016/j.tcb.2013.09.011
- NAKAUCHI Hiromitsu, KAMIYA Akihide, SUZUKI Nao, ITO Keiichi, YAMAZAKI Satoshi (2011) METHOD FOR PRODUCING CELLS INDUCED TO DIFFERENTIATE FROM PLURIPOTENT STEM CELLS PATENT COOPERATION TREATY APPLICATION, patno: WO2011071085 (A1) ― 2011-06-16 (C12N5/07)
- Amabile G, Welner RS, Nombela-Arrieta C, et al , and Tenen D.G. (2013) In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells. Blood, 121(8), 1255-1264 doi:10.1182/blood-2012-06-434407
- Suzuki, N., Yamazaki, S., Yamaguchi, T., et al. & Nakauchi, H. (2013) Generation of engraftable hematopoietic stem cells from induced pluripotent stem cells by way of teratoma formation. Molecular therapy : the journal of the American Society of Gene Therapy, 21 (7), 1424-1431, doi:10.1038/mt.2013.71
- Chou, B. K., Ye, Z., & Cheng, L. (2013). Generation and Homing of iPSC-Derived Hematopoietic Cells In Vivo. Molecular therapy: the journal of the American Society of Gene Therapy, 21(7), 1292-1293 doi:10.1038/mt.2013.129
- Y Hirami, F Osakada, K Takahashi, et al. & Takahashi M. (2009) Generation of retinal cells from mouse and human induced pluripotent stem cells. Neuroscience Letters. 458(3), 126–131 http://dx.doi.org/10.1016/j.neulet.2009.04.035
- Buchholz, D. E., Hikita, S. T., Rowland, T. J., Friedrich, A. M., Hinman, C. R., Johnson, L. V. and Clegg, D. O. (2009), Derivation of Functional Retinal Pigmented Epithelium from Induced Pluripotent Stem Cells. STEM CELLS, 27(10), 2427–2434. doi: 10.1002/stem.189
- Jin Yang, Eva Nong, Stephen H Tsang (2013) Induced pluripotent stem cells and retinal degeneration treatment. Expert Rev. Ophthalmol. 8(1), 5–8 doi: 10.1586/EOP.12.75
- Mark A. Fields, John Hwang, Jie Gong, Hui Cai, and Lucian V. (2013) Chapter 1 The Eye as a Target Organ for Stem Cell Therapy 1-30 in: Stem Cell Biology and Regenerative Medicine in Ophthalmology. Stephen H. Tsang (eds.) Springer, 2013, ISBN 146145493X, 9781461454939
- Li Y, Tsai YT, Hsu CW et al. (2012) Long-term safety and efficacy of human induced pluripotent stem cell (iPS) grafts in a preclinical model of retinitis pigmentosa Mol. Med. 18(1), 1312–1319 doi: 10.2119/molmed.2012.00242
- Stem cell therapy for RP is now offered at St. Luke’s Medical Center.
- Tzouvelekis A., Ntolios P., Bouros D. (2013) Stem Cell Treatment for Chronic Lung Diseases. Respiration; 85:179-192 DOI: 10.1159/000346525
- Wagner, D. E., Bonvillain, R. W., Jensen, T., et al. and Weiss, D. J. (2013), Can stem cells be used to generate new lungs? Ex vivo lung bioengineering with decellularized whole lung scaffolds. Respirology, 18(6): 895–911. doi: 10.1111/resp.12102
- Wong, A. P., & Rossant, J. (2013) Generation of Lung Epithelium from Pluripotent Stem Cells. Current pathobiology reports, 1(2), 137-145, DOI: 10.1007/s40139-013-0016-9
- Mou, H., Zhao, R., Sherwood, R., Ahfeldt, T et al. & Rajagopal, J. (2012). Generation of multipotent lung and airway progenitors from mouse ESCs and patient-specific cystic fibrosis iPSCs. Cell stem cell, 10(4), 385-397.doi: 10.1016/j.stem.2012.01.018
- Ghaedi, M., Calle, E. A., Mendez, J. J., et al. & Niklason, L. E. (2013). Human iPS cell–derived alveolar epithelium repopulates lung extracellular matrix. J Clin Invest. 123(11): 4950–4962. doi: 10.1172/JCI68793
- Ghaedi, M., Mendez, J. J., Bove, P. Fet al. & Niklason, L. E. (2014). Alveolar epithelial differentiation of human induced pluripotent stem cells in a rotating bioreactor. Biomaterials, 35(2), 699-710. http://dx.doi.org/10.1016/j.biomaterials.2013.10.018
- Huang S X L, Islam M N, O'Neill J. et al. & Snoeck H-W. (2013) Efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nature Biotechnology, doi:10.1038/nbt.2754
- Niu, Z., Hu, Y., Chu, Z., Yu, M., Bai, Y., Wang, L. and Hua, J. (2013), Germ-like cell differentiation from induced pluripotent stem cells (iPSCs). Cell Biochem. Funct., 31: 12-19. doi: 10.1002/cbf.2924
- Yang S, Bo J, Hu H, et al. (2012) Derivation of male germ cells from induced pluripotent stem cells in vitro and in reconstituted seminiferous tubules. Cell Prolif ; 45: 91-100.
- Panula S, Medrano JV, Kee K, et al.(2011) Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells.Hum Mol Genet ; 20: 752-62.
- Li Qian, Yu Huang, C. Ian Spencer, Amy Foley, Vasanth Vedantham, Lei Liu, Simon J. Conway, Ji-dong Fu & Deepak Srivastava. (2012) In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature, 2012; DOI: 10.1038/nature11044
- Eva Szabo,et al & Mickie Bhatia (2010) Direct conversion of human fibroblasts to multilineage blood progenitors. Nature 468, 521-526
- Jem A. Efe, et al & Sheng Ding (2011) Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy Nature Cell Biology 13, 215-222
- Ernesto Lujan, Soham Chanda, Henrik Ahlenius, Thomas C. Südhof and Marius Wernig (2012) Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells. PNAS Published online before print January 30, 2012, doi: 10.1073/pnas.1121003109
- Marc Thier, Philipp Wörsdörfer, Yenal B. Lakes, et al. (2012) Direct Conversion of Fibroblasts into Stably Expandable Neural Stem Cells. Cell Stem Cell, 22 March 2012, doi: 10.1016/j.stem.2012.03.003
- Han DW, Tapia N., Hermann A., et al. & Schöler H.R. (2012) Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors. Cell Stem Cell, April 6, 2012, doi: 10.1016/j.stem.2012.02.021
- Taylor SM , Jones PA. (1979) Multiple new phenotypes induced in 10T1 / 2 and 3T3 cells treated with 5-azacytidine. Cell; 17:771-779
- Lassar AB, Paterson BM, Weintraub H. (1986) Transfection of a DNA locus that mediates the conversion of 10T1 / 2 fibroblasts to myoblasts. Cell.; 47 (5) :649-56
- Davis RL, Weintraub H, Lassar AB. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987; 51:987-1000
- Weintraub, H., Tapscott, S. J., Davis, R. L., Thayer, M. J., Adam, M. A., Lassar, A. B. and Miller, A. D. (1989) Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell-lines by forced expression of Myod. Proc. Natl. Acad. Sci. U.S.A. 86, 5434-5438
- Thomas Vierbuchen and Marius Wernig (2011) Direct Lineage Conversions: Unnatural but useful? Nat Biotechnol.; 29 (10): 892-907. doi: 10.1038/nbt.1946
- M. R. Riddle, A. Weintraub, K. C. Q. Nguyen, D. H. Hall, J. H. Rothman. (2013) Transdifferentiation and remodeling of post-embryonic C. elegans cells by a single transcription factor. Development, 140(24), 4844-4849 doi: 10.1242/dev.103010
- Da-Woon Jung, Darren R. Williams (2011) Novel Chemically Defined Approach To Produce Multipotent Cells from Terminally Differentiated Tissue Syncytia. ACS Chemical Biology, 2011; : 110228124223097 DOI:10.1021/cb2000154
- Kim WH, et al. & Williams DR.(2012) Small molecules that recapitulate the early steps of urodele amphibian limb regeneration and confer multipotency. ACS Chem Biol. ;7(4):732-743. DOI: 10.1021/cb300127f
- Hongkai Zhang, Ian A. Wilson, and Richard A. Lerner (2012) Selection of antibodies that regulate phenotype from intracellular combinatorial antibody libraries. PNAS. 109(39), 15728-15733 doi:10.1073/pnas.1214275109
- Antibody that Transforms Bone Marrow Stem Cells Directly into Brain Cells
- Jia Xie, Hongkai Zhang, Kyungmoo Yea, and Richard A. Lerner (2013) Autocrine signaling based selection of combinatorial antibodies that transdifferentiate human stem cells PNAS; doi:10.1073/pnas.1306263110
- Xuefeng Liu, Virginie Ory, Sandra Chapman, et al. & Richard Schlegel ( 2012) ROCK Inhibitor and Feeder Cells Induce the Conditional Reprogramming of Epithelial Cells. The American Journal of Pathology, 180(2), 599-607 http://dx.doi.org/10.1016/j.ajpath.2011.10.036
- Rheinwald JG, Green H. (1975) Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975 Nov;6(3):331-43
- Hiew, Y.-L. (2011) Examining the biological consequences of DNA damage caused by irradiated J2-3T3 fibroblast feeder cells and HPV16: characterisation of the biological functions of Mll. Doctoral thesis, UCL (University College London)
- Irena Szumiel (2012) Radiation hormesis: Autophagy and other cellular mechanisms International Journal of Radiation Biology. 88(9), 619-628 doi:10.3109/09553002.2012.699698
- Hiroshi Kurosawa (2012) Application of Rho-associated protein kinase (ROCK) inhibitor to human pluripotent stem cells. Journal of Bioscience and Bioengineering, 114(6), 577–581 http://dx.doi.org/10.1016/j.jbiosc.2012.07.013
- Terunuma A, Limgala RP, Park CJ, Choudhary I, Vogel JC. (2010) Efficient procurement of epithelial stem cells from human tissue specimens using a Rho-associated protein kinase inhibitor Y-27632. Tissue Eng Part A. ;16(4):1363-1368 doi: 10.1089/ten.tea.2009.0339
- Sandra Chapman, Xuefeng Liu, Craig Meyers, Richard Schlegel, and Alison A. McBride. ( 2010) Human keratinocytes are efficiently immortalized by a Rho kinase inhibitor http://www.jci.org/articles/view/42297
- Suprynowicz F. A., Upadhyay G., Krawczyk E., et al. and Richard Schlegel. (2012) Conditionally reprogrammed cells represent a stem-like state of adult epithelial cells. PNAS, DOI: 10.1073/pnas.1213241109
- Seema Agarwal, David L. Rimm (2012) Making Every Cell Like HeLa: A Giant Step For Cell Culture. The American Journal of Pathology, 180( 2), 443-445 http://dx.doi.org/10.1016/j.ajpath.2011.12.001
- Lisanti MP, Tanowitz HB. (2012) Translational discoveries, personalized medicine, and living biobanks of the future. The American Journal of Pathology, 2012 Apr;180(4):1334-6 http://www.sciencedirect.com/science/article/pii/S0002944012000971
- Hang Yuan, Scott Myers, Jingang Wang, et al & Richard Schlegel. (2012) Use of Reprogrammed Cells to Identify Therapy for Respiratory Papillomatosis. New England Journal of Medicine; 367 (13): 1220-1227 DOI:10.1056/NEJMoa1203055
- Palechor-Ceron N, Suprynowicz FA, Upadhyay G, Dakic A, Minas T, Simic V, Johnson M, Albanese C, Schlegel R, Liu X. (2013) Radiation Induces Diffusible Feeder Cell Factor(s) That Cooperate with ROCK Inhibitor to Conditionally Reprogram and Immortalize Epithelial Cells. Am J Pathol. 2013 Dec;183(6):1862-70. doi: 10.1016/j.ajpath.2013.08.009
- Sukhbir Kaur, David R. Soto-Pantoja, Erica V. Stein et al. & David D. Roberts.( 2013) Thrombospondin-1 Signaling through CD47 Inhibits Self-renewal by Regulating c-Myc and Other Stem Cell Transcription Factors. Scientific Reports; 3, Article number: 1673 DOI:10.1038/srep01673
- Leo Kurian, Ignacio Sancho-Martinez, Emmanuel Nivet, et al. & Juan Carlos Izpisua Belmonte (2012) Conversion of human fibroblasts to angioblast-like progenitor cells. Nature Methods. doi:10.1038/nmeth.2255
- Wang, Y. C., Nakagawa, M., Garitaonandia. et al. & Loring, J. F. (2011). Specific lectin biomarkers for isolation of human pluripotent stem cells identified through array-based glycomic analysis.Cell research, 21 (11 ) , 1551-1563 . doi: 10.1038/cr.2011.148
- Hasehira, K., Tateno, H., Onuma, Y., Ito, Y., Asashima, M., & Hirabayashi, J. ( 2012). Structural and Quantitative Evidence for Dynamic Glycome Shift on Production of Induced Pluripotent Stem Cells. Molecular & Cellular Proteomics, 11 (12 ) 1913-1923 . doi: 10.1074/mcp.M112.020586
- Becker-Kojic, Z. A., & Terness, P. (2002). A novel human erythrocyte GPI anchored glycoprotein ACA. Isolation, purification, primary structure determination, molecular parameters of its lipid structure. . Journal of Biological Chemistry, 277, 40472-40478 . doi: 10.1074/jbc.M202416200
- ZABecker-Kojič, J . Ureña-Peralta, R.Saffrich et al. & M.Stojkovič ( 2013 ) A new glycoprotein ACA - the main regulator of human hematopoiesis . CELL TECHNOLOGIES IN BIOLOGY AND MEDICINE , 9 (2 ) , 69-84 (rus.)
- ZABecker-Kojič, JRUreña-Peralta, I.Zipančić, et al. & M.Stojkovič ( 2013 ) Activation of surface glycoprotein ACA induced pluripotent hematopoietic progenitor cells. CELL TECHNOLOGIES IN BIOLOGY AND MEDICINE , 9 (2 ) , 85-101 (rus.)
- Mikkola, M. ( 2013 ) Human pluripotent stem cells: glycomic approaches for culturing and characterization. http://urn.fi/URN:ISBN 978-952-10-8444-7
- Torben Redmer, Sebastian Diecke, Tamara Grigoryan, Angel Quiroga-Negreira, Walter Birchmeier, Daniel Besser (2011) E-cadherin is crucial for embryonic stem cell pluripotency and can replace OCT4 during somatic cell reprogramming. EMBO reports , 12, 720 - 726, doi:10.1038/embor.2011.88
- Bedzhov, I., Alotaibi, H., Basilicata, M. F. et al. & Stemmler, M. P. (2013). Adhesion, but not a specific cadherin code, is indispensable for ES cell and induced pluripotency. Stem cell research, 11(3), 1250-1263. http://dx.doi.org/10.1016/j.scr.2013.08.009
- Guannan Su, Yannan Zhao, Jianshu Wei, et al. & Jianwu Dai (2013) Direct conversion of fibroblasts into neural progenitor-like cells by forced growth into 3D spheres on low attachment surfaces. Biomaterials, 34(24), 5897–5906 http://dx.doi.org/10.1016/j.biomaterials.2013.04.040
- Timothy L. Downing, Jennifer Soto, Constant Morez, Timothee Houssin, Ashley Fritz, Falei Yuan, Julia Chu, Shyam Patel, David V. Schaffer, Song Li.(2013) Biophysical regulation of epigenetic state and cell reprogramming. Nature Materials, DOI: 10.1038/nmat3777
- Patricia Murray, Marina Prewitz, Isabel Hopp, et al. (2013) The self-renewal of mouse embryonic stem cells is regulated by cell–substratum adhesion and cell spreading. The International Journal of Biochemistry & Cell Biology, 45(11), 2698–2705 http://dx.doi.org/10.1016/j.biocel.2013.07.001
- Guilak, F., Cohen, D. M., Estes, B. T., et al. & Chen, C. S. (2009) Control of stem cell fate by physical interactions with the extracellular matrix. Cell stem cell, 5(1), 17-26. doi: 10.1016/j.stem.2009.06.016
- Worley, K., Certo, A., & Wan, L. Q. (2013). Geometry–Force Control of Stem Cell Fate. BioNanoScience, 3(1), 43-51. DOI: 10.1007/s12668-012-0067-0
- Zhang W, Duan S, Li Y. et al. and Jing Qu (2012) Converted neural cells: induced to a cure? Protein Cell; 3(2), 91–97. DOI: 10.1007/s13238-012-2029-2
- Yang N, Ng YH, Pang ZP, Sudhof TC, Wernig M.(2011) Induced neuronal cells: how to make and define a neuron. Cell Stem Cell; 9(6), 517–525. doi: 10.1016/j.stem.2011.11.015
- Sheng C, Zheng Q, Wu J, et al. and Qi Zhou (2012) Generation of dopaminergic neurons directly from mouse fibroblasts and fibroblast-derived neural progenitors. Cell Res; 22:769–772. doi:10.1038/cr.2012.32
- Maucksch, C., E. Firmin, et al. (2012). "Non-viral generation of neural precursor-like cells from adult human fibroblasts." J Stem Cells Regen Med 8(3): 1-9.
- Ring K L, Leslie M. Tong L M, Balestra M E et al. & Yadong Huang (2012) Direct Reprogramming of Mouse and Human Fibroblasts into Multipotent Neural Stem Cells with a Single Factor. Cell Stem Cell, 11(1), 100-109 doi: 10.1016/j.stem.2012.05.018
- Liu G-H , Yi F, Suzuki K, Qu J. and Izpisua Belmonte J C. (2012) Induced neural stem cells: a new tool for studying neural development and neurological disorders. Cell Research 22, 1087–1091. doi:10.1038/cr.2012.73
- Olof Torper, Ulrich Pfisterer, Daniel A. Wolf, et al. and Malin Parmar (2013) Generation of induced neurons via direct conversion in vivo. PNAS, DOI:10.1073/pnas.1303829110
- Fadi J Najm, Angela M Lager, Anita Zaremba, et al. & Paul J Tesar (2013) Transcription factor–mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells. Nature Biotechnology, doi:10.1038/nbt.2561
- Nan Yang, J Bradley Zuchero, Henrik Ahlenius, et al. & Marius Wernig (2013) Generation of oligodendroglial cells by direct lineage conversion. Nature Biotechnology, doi:10.1038/nbt.2564
- Chunhui (2012) Turning cardiac fibroblasts into cardiomyocytes in vivo Trends in Molecular Medicine, doi:10.1016/j.molmed.2012.06.009
- Ji-Dong Fu, Nicole R. Stone, Lei Liu, et al. & Deepak Srivastava (2013) Direct Reprogramming of Human Fibroblasts toward a Cardiomyocyte-like State. Stem Cell Reports, doi: 10.1016/j.stemcr.2013.07.005
- Chen J X., Krane M, Deutsch M-A, et al. and Sean M. Wu (2012)Inefficient Reprogramming of Fibroblasts into Cardiomyocytes Using Gata4, Mef2c, and Tbx5. Circulation Research.;111: 50-55, doi:10.1161/CIRCRESAHA.112.270264
- Paul W. Burridge, Gordon Keller, Joseph D. Gold, Joseph C. Wu (2012) Production of De Novo Cardiomyocytes: Human Pluripotent Stem Cell Differentiation and Direct Reprogramming. Review Article. Cell Stem Cell, 10 (1), 16-28
- Carpenter L. et al. and Watt S. M. (2012) Efficient Differentiation of Human Induced Pluripotent Stem Cells Generates Cardiac Cells That Provide Protection Following Myocardial Infarction in the Rat. Stem Cells and Development. 21 (6): 977-986. doi: 10.1089/scd.2011.0075.
- Satsuki Yamada, Timothy J. Nelson, Garvan C. Kane et al. & Andre Terzic (2013) iPS Cell Intervention Rescues Wall Motion Disparity Achieving Biological Cardiac Resynchronization Post-Infarction.The Journal of Physiology, 591, 4335-4349.; DOI:10.1113/jphysiol.2013.252288
- Lian X, Hsiao C, Gisela Wilson, et al and Palecek S P. (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. PNAS 2012 109 (27) E1848-E1857, doi: 10.1073/pnas.1200250109.
- Willems E, Cabral-Teixeira J, et al. & Mark Mercola. (2012) Small Molecule-Mediated TGF-β Type II Receptor Degradation Promotes Cardiomyogenesis in Embryonic Stem Cells. Cell Stem Cell,; 11 (2): 242-252 DOI: 10.1016/j.stem.2012.04.025
- Tung-Ying Lu, Bo Lin, Jong Kim, et al. & Lei Yang (2013) Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells. Nature Communications, 4, Article number: 2307 doi:10.1038/ncomms3307
- Caroline E. Hendry, Jessica M. Vanslambrouck, Jessica Ineson, et al. and Melissa H. Little (2013) Direct Transcriptional Reprogramming of Adult Cells to Embryonic Nephron Progenitors. JASN ASN.2012121143; ,doi:10.1681/ASN.2012121143
- Xinaris C, Benedetti V, Rizzo P, et al. and Giuseppe Remuzzi (2012) In vivo maturation of functional renal organoids formed from embryonic cell suspensions. J Am Soc Nephrol 23: 1857–1868, doi: 10.1681/ASN.2012050505
- Yin L, Ohanyan V, Pung Y F, and Chilian W M. (2012) Induction of Vascular Progenitor Cells From Endothelial Cells Stimulates Coronary Collateral Growth. Circulation Research.;110:241-252, doi:10.1161/CIRCRESAHA.111.250126
- Quijada P, Toko H, Fischer K M., et al. and Sussman M, A. (2012) Preservation of Myocardial Structure Is Enhanced by Pim-1 Engineering of Bone Marrow Cells. Circulation Research. ;111:77-86, doi:10.1161/CIRCRESAHA.112.265207
- Mohsin S, Mohsin K, Toko H, et al & Sussman M A. (2012) Human Cardiac Progenitor Cells Engineered With Pim-I Kinase Enhance Myocardial Repair. J Am Coll Cardiol. 2012; doi:10.1016/j.jacc.2012.04.047
- American Heart Association (2012, July 25). Adult stem cells from liposuction used to create blood vessels in the lab. ScienceDaily.
- ZZ Wang, P Au, T Chen, et al. (2007) Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo, Nature Biotechnology 25, 317-318, doi:10.1038/nbt1287
- Rekha Samuel, Laurence Daheron, Shan Liao, et al. and Rakesh K. Jain (2013 ) Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells. PNAS doi:10.1073/pnas.1310675110
- Lior Zangi, Kathy O Lui, Alexander von Gise, et al. & Kenneth R Chien.( 2013) Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction. Nature Biotechnology,; DOI:10.1038/nbt.2682
- Carlos-Filipe Pereira, Betty Chang, Jiajing Qiu et al & Kateri Moore (2013) Induction of a Hemogenic Program in Mouse Fibroblasts. Cell Stem Cell, http://dx.doi.org/10.1016/j.stem.2013.05.024
- Zeuner, A., Martelli, F., et al. and Migliaccio, A. R. (2012), Concise Review: Stem Cell-Derived Erythrocytes as Upcoming Players in Blood Transfusion. STEM CELLS, 30: 1587–1596. doi: 10.1002/stem.1136
- Hirose Sho-ichi, Takayama Naoya, Nakamura Sou, et al. & Eto Koji (2013) Immortalization of Erythroblasts by c-MYC and BCL-XL Enables Large-Scale Erythrocyte Production from Human Pluripotent Stem Cells. Stem Cell Reports, doi: 10.1016/j.stemcr.2013.10.010
- Giarratana MC, Rouard H, Dumont A, et al & Luc Douay (2011) Proof of principle for transfusion of in vitro generated red blood cells. Blood; 118(19): 5071-5079. doi: 10.1182/blood-2011-06-362038.
- Ladan Kobari, Frank Yates, Noufissa Oudrhiri et al. and Luc Douay (2012) Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model. Haematologica. 2012; 97:xxx DOI: 10.3324/haematol.2011.055566
- Keerthivasan Ganesan , Wickrema A, and Crispino J D (2011) Erythroblast Enucleation Stem Cells Int.; 2011: 139851. doi: 10.4061/2011/139851
- Emmanuel Olivier, Caihong Qiu, Eric E. Bouhassira (2012) Protocols and Manufacturing for Cell-Based TherapiesNovel, High-Yield Red Blood Cell Production Methods from CD34-Positive Cells Derived from Human Embryonic Stem, Yolk Sac, Fetal Liver, Cord Blood, and Peripheral Blood Stem Cells Trans Med first published on August 2, 2012;doi:10.5966/sctm.2012-0059
- Brenden W. Smith, Sarah S. Rozelle, Amy Leung, et al and George J. Murphy (2013) The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation. Blood, blood-2012-11-466722, doi: 10.1182/blood-2012-11-466722
- Figueiredo C, Goudeva L., Horn P. A., et al and Seltsam A. (2010) Generation of HLA-deficient platelets from hematopoietic progenitor cells. Transfusion.; 50(8): 1690-701. doi: 10.1111/j.1537-2995.2010.02644.x.
- Riddell, S.R. & Greenberg, P.D. (1995) Principles for adoptive T cell therapy of human viral diseases. Annu. Rev. Immunol. 13, 545–586 DOI: 10.1146/annurev.iy.13.040195.002553
- Toshinobu Nishimura, Shin Kaneko, Ai Kawana-Tachikawa et al. & Hiromitsu Nakauchi (2013) Generation of rejuvenated antigen-specific T cells by pluripotency reprogramming and redifferentiation. Cell Stem Cell, 12(1), 114-126 DOI: 10.1016/j.stem.2012.11.002
- Raul Vizcardo, Kyoko Masuda, Daisuke Yamada, et al. & Hiroshi Kawamoto (2013) Regeneration of Human Tumor Antigen-Specific T Cells from iPSCs Derived from Mature CD8+ T Cells . Cell Stem Cell, 12(1), 31-36 DOI: http://dx.doi.org/10.1016/j.stem.2012.12.006
- Joseph G. Crompton, Mahendra Rao, Nicholas P. Restifo (2013) Memoirs of a Reincarnated T Cell. Cell Stem Cell, 12(1), 6-8 DOI: 10.1016/j.stem.2012.12.009
- Lei F, Haque R, Xiong X, Song J. (2012) Directed differentiation of induced pluripotent stem cells towards T lymphocytes. J Vis Exp. ;(63):e3986. doi: 10.3791/3986
- Sadelain, M., Brentjens, R. & Riviere, I. (2013). The basic principles of chimeric antigen receptor design. Cancer Discov. 3, 388–398 doi: 10.1158/2159-8290.CD-12-054
- Maria Themeli, Christopher C Kloss, Giovanni Ciriello, et al. & Michel Sadelain (2013) Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy. Nature Biotechnology, doi:10.1038/nbt.2678
- Karsten A. Pilones, Joseph Aryankalayil, and Sandra Demaria (2012) Invariant NKT Cells as Novel Targets for Immunotherapy in Solid Tumors. Clinical and Developmental Immunology, 2012 , Article ID 720803, doi:10.1155/2012/720803
- Watarai H, Yamada D, Fujii S, Taniguchi M, Koseki H. (2012) Induced pluripotency as a potential path towards iNKT cell-mediated cancer immunotherapy. Int J Hematol. ;95(6):624-631. doi: 10.1007/s12185-012-1091-0
- M Haruta, Y Tomita, A Yuno, et al. and S Senju (2012) TAP-deficient human iPS cell-derived myeloid cell lines as unlimited cell source for dendritic cell-like antigen-presenting cells. Gene Therapy , doi:10.1038/gt.2012.59
- Peng Y, Huang S, Cheng B, et al. and Fu X. (2012) Mesenchymal stem cells: A revolution in therapeutic strategies of age-related diseases Review Article. Ageing Research Reviews, , Available online 30 April 2012, .doi.org/10.1016/j.arr.2012.04.005
- Bieback K, Kern S, Kocaomer A et al. (2008) Comparing mesenchymal stromal cells from different human tissues: Bone marrow, adipose tissue and umbilical cord blood. Biomed Mater Eng; 18:S71–S76
- Stolzing A, Jones E, McGonagle D et al. (2008) Age-related changes in human bone marrow derived mesenchymal stem cells: Consequences for cell therapies. Mech Ageing Dev;129:163–173
- Irina Eberle, Mohsen Moslem, Reinhard Henschler, Tobias Cantz (2012) Engineered MSCs from Patient-Specific iPS Cells. Advances in Biochemical Engineering Biotechnology
- Chen Y S, Pelekanos R A., Ellis R L., et al and Nicholas M. Fisk (2012) Small Molecule Mesengenic Induction of Human Induced Pluripotent Stem Cells to Generate Mesenchymal Stem/Stromal Cells Stem Cells Trans Med published online February 7, 2012 doi:10.5966/sctm.2011-0022
- Ruenn Chai Lai, Ronne Wee Yeh Yeo, Soon Sim Tan, Bin Zhang, et al. and Sai Kiang Lim (2013) Mesenchymal Stem Cell Exosomes: The Future MSC-Based Therapy? In: Mesenchymal Stem Cell Therapy. Chase, Lucas G.; Vemuri, Mohan C. (Eds.). 39-61 DOI 10.1007/978-1-62703-200-1_3
- Ruenn Chai Lai, Ronne Wee Yeh Yeo, Kok Hian Tan, Sai Kiang Lim (2013) Exosomes for drug delivery — a novel application for the mesenchymal stem cell. Biotechnology Advances.http://dx.doi.org/10.1016/j.biotechadv.2012.08.008
- Ronne Wee Yeh Yeoa, Ruenn Chai Laia, Bin Zhanga, et al. & Sai Kiang Lim (2012)Mesenchymal stem cell: An efficient mass producer of exosomes for drug delivery. Advanced Drug Delivery Reviewshttp://dx.doi.org/10.1016/j.addr.2012.07.001
- Nobuyoshi Kosaka, Fumitaka Takeshita, Yusuke Yoshioka, et al. & Takahiro Ochiya (2012) Exosomal tumor-suppressive microRNAs as novel cancer therapy: «Exocure» is another choice for cancer treatment. Advanced Drug Delivery Reviewshttp://dx.doi.org/10.1016/j.addr.2012.07.011
- Poloni A, Maurizi G, Leoni P, et al. & Cinti S (2012) Human Dedifferentiated Adipocytes Show Similar Properties to Bone Marrow-Derived Mesenchymal Stem Cells. Stem Cells. ;30(5):965-74. doi: 10.1002/stem.1067.
- Shen JF, Sugawara A, Yamashita J, Ogura H, Sato S. (2011) Dedifferentiated fat cells: an alternative source of adult multipotent cells from the adipose tissues. Int J Oral Sci.;3(3):117-24
- Sara M. Melief, Jaap Jan Zwaginga, Willem E. Fibbe and Helene Roelofs ( 2013) Adipose Tissue-Derived Multipotent Stromal Cells Have a Higher Immunomodulatory Capacity Than Their Bone Marrow-Derived Counterparts. Stem Cells Trans Med May 2013 sctm.2012-0184 doi:10.5966/sctm.2012-0184
- Cheng, A., Hardingham, T. E., & Kimber, S. J. (2013). Generating Cartilage Repair from Pluripotent Stem Cells. Tissue Engineering Part B: Reviews. doi:10.1089/ten.teb.2012.0757.
- Outani H, Okada M, Yamashita A, Nakagawa K, Yoshikawa H, et al. (2013) Direct Induction of Chondrogenic Cells from Human Dermal Fibroblast Culture by Defined Factors. PLoS ONE 8(10): e77365. doi:10.1371/journal.pone.0077365
- Keisuke Okita, Tatsuya Yamakawa, Yasuko Matsumura, et al. & Shinya Yamanaka (2013) An Efficient Non-viral Method to Generate Integration-Free Human iPS Cells from Cord Blood and Peripheral Blood Cells. STEM CELLS, DOI: 10.1002/stem.1293
- Imbisaat Geti, Mark L. Ormiston, Foad Rouhani, et al & Nicholas W. Morrell (2012) A Practical and Efficient Cellular Substrate for the Generation of Induced Pluripotent Stem Cells from Adults: Blood-Derived Endothelial Progenitor Cells. Stem Cells Trans Med. sctm.2012-0093 doi:10.5966/sctm.2012-0093
- Judith Staerk, Meelad M. Dawlaty, Qing Gaoet al. and Rudolf Jaenisch (2010) Reprogramming of Human Peripheral Blood Cells to Induced Pluripotent Stem Cells. Cell Stem Cell, 7(1), 20-24 doi:10.1016/j.stem.2010.06.002
- Park TS, Huo JS, Peters A, Talbot CC Jr, Verma K, et al. (2012) Growth Factor-Activated Stem Cell Circuits and Stromal Signals Cooperatively Accelerate Non-Integrated iPSC Reprogramming of Human Myeloid Progenitors. PLoS ONE 7(8): e42838. doi:10.1371/journal.pone.0042838
- Katsuhiro Yoshikawa, Motoko Naitoh, Hiroshi Kubota, et al. (2013) Multipotent stem cells are effectively collected from adult human cheek skin. Biochemical and Biophysical Research Communications, 431(1), 104–110 http://dx.doi.org/10.1016/j.bbrc.2012.12.069
- Zhou T, Benda C, Duzinger S, Et al & Esteban MA(2011) Generation of induced pluripotent stem cells from urine. J Am Soc Nephrol 22: 1221—1228
- Ting Zhou, Christina Benda, Sarah Dunzinger, et al. & Miguel A Esteban (2012) Generation of human induced pluripotent stem cells from urine samples. Nature Protocols. 7(12), 2080–2089 doi:10.1038/nprot.2012.115
- Lihui Wang, Linli Wang, Wenhao Huang, & Duanqing Pei (2012) Generation of integration-free neural progenitor cells from cells in human urine. Nature Methods, doi:10.1038/nmeth.2283
- . Cai J, Zhang Y, Liu P, Chen S, Wu X, Sun Y, Li A, Huang K et al (2013)Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells. Cell Regeneration , 2:6 doi:10.1186/2045-9769-2-6
- Shantaram Bharadwaj, Guihua Liu, Yingai Shi, et al. & Yuanyuan Zhang (2013) Multi-Potential Differentiation of Human Urine-Derived Stem Cells: Potential for Therapeutic Applications in Urology. STEM CELLS, DOI: 10.1002/stem.1424
- Yimei Wang1, Jinyu Liu1, Xiaohua Tan1, et al. and Yulin Li (2012) Induced Pluripotent Stem Cells from Human Hair Follicle Mesenchymal Stem Cells. Stem Cell Reviews and Reports, doi:10.1007/s12015-012-9420-5
- Schnabel L. V, Abratte C. M., Schimenti J. C, et al. and Fortier L. A. (2012) Genetic background affects induced pluripotent stem cell generation. Stem Cell Research & Therapy 2012, 3:30 doi:10.1186/scrt121
- Panopoulos AD, Ruiz S, Yi F, Herrerías A, Batchelder EM, Izpisua Belmonte JC.(2011) Rapid and highly efficient generation of induced pluripotent stem cells from human umbilical vein endothelial cells. PLoS One;6:e19743
- J.M. Polo, S. Liu, M.E. Figueroa, et al. & Konrad Hochedlinger (2010) Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol, 28, 848–855 doi:10.1038/nbt.1667
- Miura K, Okada Y, Aoi T, Okada A, et al & Yamanaka S.(2009) Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol.;27:743-745
- Liang Y, Zhang H, Feng QS et al. (2012) The Propensity for Tumorigenesis in Human Induced Pluripotent Stem Cells is Correlated with Genomic Instability. Chin J Cancer. doi: 10.5732/cjc.012.10065. [Epub ahead of print]
- K. Kim, A. Doi, B. Wen, K. Ng, R. Zhao, P. Cahan, J. Kim, M.J. Aryee, H. Ji, L.I. Ehrlich et al. (2010) Epigenetic memory in induced pluripotent stem cells. Nature, 467, 285–290 doi:10.1038/nature09342
- K. Kim, R. Zhao, A. Doi,et al. (2011) Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nat Biotechnol, 29, pp. 1117–1119
- O. Bar-Nur, H.A. Russ, S. Efrat, N. Benvenisty (2011) Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell, 9 , 17–23 http://dx.doi.org/10.1016/j.stem.2011.06.007
- Denker H-W.( 2012) Time to Reconsider Stem Cell Induction Strategies. Cells.; 1(4):1293-1312. doi:10.3390/cells1041293