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Regenerative medicine

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A colony of human embryonic stem cells

Regenerative medicine is a branch of translational research[1] in tissue engineering and molecular biology which deals with the "process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function".[2] This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs.[3]

Regenerative medicine also includes the possibility of growing tissues and organs in the laboratory and implanting them when the body cannot heal itself. If a regenerated organ's cells would be derived from the patient's own tissue or cells, this would potentially solve the problem of the shortage of organs available for donation, and the problem of organ transplant rejection.[4][5][6]

Some of the biomedical approaches within the field of regenerative medicine may involve the use of stem cells.[7] Examples include the injection of stem cells or progenitor cells obtained through directed differentiation (cell therapies); the induction of regeneration by biologically active molecules administered alone or as a secretion by infused cells (immunomodulation therapy); and transplantation of in vitro grown organs and tissues (tissue engineering).[8][9]

History

An important advancement contributing to regenerative medicine occurred in 1956.[10] John Bertrand Gurdon won a Nobel prize for being the first to successfully replace the DNA from a frog's egg cell with the DNA from an intestinal cell. These transformed egg cells continued to develop into completely normal tadpoles, showing that the DNA in an individual's cells is all the same, despite what kind of cell it is.[10]

The term "regenerative medicine" was first used in a 1992 article on hospital administration by Leland Kaiser. Kaiser’s paper closes with a series of short paragraphs on future technologies that will impact hospitals. One paragraph had "Regenerative Medicine" as a bold print title and stated, "A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems."[11][12]

The widespread use of the term regenerative medicine is attributed to William A. Haseltine (founder of Human Genome Sciences).[13] Haseltine was briefed on the project to isolate human embryonic stem cells and embryonic germ cells at Geron Corporation in collaboration with researchers at the University of Wisconsin-Madison and Johns Hopkins School of Medicine. He recognized that these cells' unique ability to differentiate into all the cell types of the human body (pluripotency) had the potential to develop into a new kind of regenerative therapy.[14][15] Explaining the new class of therapies that such cells could enable, he used the term "regenerative medicine" in the way that it is used today: "an approach to therapy that ... employs human genes, proteins and cells to re-grow, restore or provide mechanical replacements for tissues that have been injured by trauma, damaged by disease or worn by time" and "offers the prospect of curing diseases that cannot be treated effectively today, including those related to aging." [16] From 1995 to 1998 Michael D. West, PhD, organized and managed the research between Geron Corporation and its academic collaborators James Thomson at the University of Wisconsin-Madison and John Gearhart of Johns Hopkins University that led to the first isolation of human embryonic stem and human embryonic germ cells, respectively.[17]

Dr. Stephen Badylak, a Research Professor in the Department of Surgery and director of Tissue Engineering at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, developed a process for scraping cells from the lining of a pig's bladder, decellularizing (removing cells to leave a clean extracellular structure) the tissue and then drying it to become a sheet or a powder. This extracellular matrix powder was used to regrow the finger of Lee Spievak, who had severed half an inch of his finger after getting it caught in a propeller of a model plane.[18][19][20][dubious – discuss] As of 2011, this new technology is being employed by the military on U.S. war veterans in Texas, as well as for some civilian patients. Nicknamed "pixie-dust," the powdered extracellular matrix is being used to successfully regenerate tissue lost and damaged due to traumatic injuries.[21]

In June 2008, at the Hospital Clínic de Barcelona, Professor Paolo Macchiarini and his team, of the University of Barcelona, performed the first tissue engineered trachea (wind pipe) transplantation. Adult stem cells were extracted from the patient's bone marrow, grown into a large population, and matured into cartilage cells, or chondrocytes, using an adaptive method originally devised for treating osteoarthritis. The team then seeded the newly grown chondrocytes, as well as epithileal cells, into a decellularised (free of donor cells) tracheal segment that was donated from a 51-year-old transplant donor who had died of cerebral hemorrhage. After four days of seeding, the graft was used to replace the patient's left main bronchus. After one month, a biopsy elicited local bleeding, indicating that the blood vessels had already grown back successfully.[22][23]

In 2009, the SENS Foundation was launched, with its stated aim as "the application of regenerative medicine – defined to include the repair of living cells and extracellular material in situ – to the diseases and disabilities of ageing." [24]

In 2012, Professor Paolo Macchiarini and his team improved upon the 2008 implant by transplanting a laboratory-made trachea seeded with the patient's own cells.[25]

On September 12, 2014, surgeons at the Institute of Biomedical Research and Innovation Hospital in Kobe, Japan, transplanted a 1.3 by 3.0 millimeter sheet of retinal pigment epithelium cells, which were differentiated from iPS cells through Directed differentiation, into an eye of an elderly woman, who suffers from age-related macular degeneration.[26]

Cord blood

Because a person's own (autologous) cord blood stem cells can be safely infused back into that individual without being rejected by the body's immune system – and because they have unique characteristics compared to other sources of stem cells – they are an increasing focus of regenerative medicine research.

The use of cord blood stem cells in treating conditions such as brain injury[27] and Type 1 Diabetes[28] is already being studied in humans, and earlier stage research is being conducted for treatments of stroke,[29][30] and hearing loss.[31]

Current estimates indicate that approximately 1 in 3 Americans could benefit from regenerative medicine.[32] With autologous (the person's own) cells, there is no risk of the immune system rejecting the cells.

Researchers are exploring the use of cord blood stem cells for a spectrum of regenerative medicine applications, including the following:

Type 1 diabetes

A clinical trial under way at the University of Florida is examining how an infusion of autologous cord blood stem cells into children with Type 1 diabetes will impact metabolic control over time, as compared to standard insulin treatments. Preliminary results demonstrate that an infusion of cord blood stem cell is safe and may provide some slowing of the loss of insulin production in children with type 1 diabetes.[33]

Cardiovascular

The stem cells found in a newborn's umbilical cord blood are holding great promise in cardiovascular repair. Researchers are noting several positive observations in pre-clinical animal studies. Thus far, in animal models of myocardial infarction, cord blood stem cells have shown the ability to selectively migrate to injured cardiac tissue, improve vascular function and blood flow at the site of injury, and improve overall heart function.[32]

Central nervous system

Research has demonstrated convincing evidence in animal models that cord blood stem cells injected intravenously have the ability to migrate to the area of brain injury, alleviating mobility related symptoms.[34][35] Also, administration of human cord blood stem cells into animals with stroke was shown to significantly improve behavior by stimulating the creation of new blood vessels and neurons in the brain.[36]

This research also lends support for the pioneering clinical work at Duke University, focused on evaluating the impact of autologous cord blood infusions in children diagnosed with cerebral palsy and other forms of brain injury. This study is examining if an infusion of the child's own cord blood stem cells facilitates repair of damaged brain tissue, including many with cerebral palsy. To date, more than 100 children have participated in the experimental treatment – many whose parents are reporting good progress.[37]

Another report published encouraging results in 2 toddlers with cerebral palsy where autologous cord blood infusion was combined with G-CSF.[38]

As these clinical and pre-clinical studies demonstrate, cord blood stem cells will likely be an important resource as medicine advances toward harnessing the body's own cells for treatment. The field of regenerative medicine can be expected to benefit greatly as additional cord blood stem cell applications are researched and more people have access to their own preserved cord blood. [39]

On May 17, 2012, Osiris Therapeutics announced that Canadian health regulators approved Prochymal, a drug for acute graft-versus-host disease in children who have failed to respond to steroid treatment. Prochymal is the first stem cell drug to be approved anywhere in the world for a systemic disease. Graft-versus-host disease, a potentially fatal complication from bone marrow transplant, involves the newly implanted cells attacking the patient's body.[40]

See also

References

  1. ^ New health facility aims to translate stem cell science into therapies | USC News
  2. ^ Regenerative Medicine, 2008, 3(1), 1–5 [47]
  3. ^ Health News - UM Leads in the Field of Regenerative Medicine: Moving from Treatments to Cures
  4. ^ "Regenerative Medicine. NIH Fact sheet 092106.doc" (PDF). September 2006. Retrieved 2010-08-16.
  5. ^ Mason C; Dunnill P (January 2008). "A brief definition of regenerative medicine". Regenerative Medicine. 3 (1): 1–5. doi:10.2217/17460751.3.1.1. PMID 18154457.
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  8. ^ Stoick-Cooper CL; Moon RT; Weidinger G (June 2007). "Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine". Genes & Development. 21 (11): 1292–315. doi:10.1101/gad.1540507. PMID 17545465.
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  25. ^ "Surgeons Implant Synthetic Trachea In Baltimore Man". nytimes.com. 2012-01-12. Retrieved 2012-02-23.
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  31. ^ Revoltella RP (2008). "Cochlear repair by transplantation of human cord blood CD133+ cells to nod-scid mice made deaf with kanamycin and noise". Cell Transplant. 17 (6): 665–678. doi:10.3727/096368908786092685. PMID 18819255. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
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  33. ^ Haller MJ (2008). "Autologous umbilical cord blood infusion for type 1 diabetes. www.york.ac.uk/res/cordblood". Exp. Hematol. 36 (6): 710–715. doi:10.1016/j.exphem.2008.01.009. PMC 2444031. PMID 18358588. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
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  35. ^ Meier, C.; Middelanis, Johannes; Wasielewski, Bianca; Neuhoff, Sandra; Roth-Haerer, Astrid; Gantert, Markus; Dinse, Hubert R.; Dermietzel, Rolf; Jensen, Arne (2006). "Spastic paresis after perinatal brain damage in rats is reduced by human cord blood mononuclear cells". Pediatr. Res. 59 (2): 244–249. doi:10.1203/01.pdr.0000197309.08852.f5. PMID 16439586.
  36. ^ Taguchi A (2004). "Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model". J. Clin. Invest. 114 (3): 330–338. doi:10.1172/JCI20622. PMC 484977. PMID 15286799. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  37. ^ Sun J (2010). "Differences in quality between privately and publicly banked umbilical cord blood units: a pilot study of autologous cord blood infusion in children with acquired neurologic disorders". Transfusion. 50 (9): 1980–1987. doi:10.1111/j.1537-2995.2010.02720.x. PMID 20546200. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  38. ^ Papadopoulos KI (2011). "Safety and feasibility of autologous umbilical cord blood transfusion in 2 toddlers with cerebral palsy and the role of low dose granulocyte-colony stimulating factor injections". Restor Neurol Neurosci. 29 (1): 17–22. doi:10.3233/RNN-2011-0572. PMID 21335665. {{cite journal}}: Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  39. ^ "Steenblock Research Institute, umbilical cord stem cell therapy".
  40. ^ "World's First Stem-Cell Drug Approval Achieved in Canada". The National Law Review. Drinker Biddle & Reath LLP. 2012-06-12. Retrieved 2012-07-01.

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