Regenerative medicine is a branch of translational research 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". 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.
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.
Some of the biomedical approaches within the field of regenerative medicine may involve the use of stem cells. 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).
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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."
The widespread use of the term regenerative medicine is attributed to William A. Haseltine (founder of Human Genome Sciences). 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. 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". 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.
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.
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". 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.
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.
In 2016, Paolo Macchiarini was fired from Karolinska University in Sweden due to falsified test results and lies. The TV-show Experimenten aired on Swedish Television and detailed all the lies and falsified results.
Extracellular matrix materials are commercially available and are used in reconstructive surgery, treatment of chronic wounds, and some orthopedic surgeries; as of January 2017 clinical studies were under way to use them in heart surgery to try to repair damaged heart tissue.
Though uses of cord blood beyond blood and immunological disorders is speculative, some research has been done in other areas. Any such potential beyond blood and immunological uses is limited by the fact that cord cells are hematopoietic stem cells (which can differentiate only into blood cells), and not pluripotent stem cells (such as embryonic stem cells, which can differentiate into any type of tissue). Cord blood has been studied as a treatment for diabetes. However, apart from blood disorders, the use of cord blood for other diseases is not a routine clinical modality and remains a major challenge for the stem cell community.
Along with cord blood, Wharton's jelly and the cord lining have been explored as sources for mesenchymal stem cells (MSC), and as of 2015 had been studied in vitro, in animal models, and in early stage clinical trials for cardiovascular diseases, as well as neurological deficits, liver diseases, immune system diseases, diabetes, lung injury, kidney injury, and leukemia.
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Non-technical further reading
- Regenerative Medicine, gives more details about Regenerative Stem Cells.
- Cogle CR; Guthrie SM; Sanders RC; Allen WL; Scott EW; Petersen BE (August 2003). "An overview of stem cell research and regulatory issues". Mayo Clinic Proceedings. 78 (8): 993–1003. doi:10.4065/78.8.993. PMID 12911047.
- Kevin Strange and Viravuth Yin, "A Shot at Regeneration: A once abandoned drug compound shows an ability to rebuild organs damaged by illness and injury", Scientific American, vol. 320, no. 4 (April 2019), pp. 56–61.
Technical further reading
- Metallo CM; Azarin SM; Ji L; de Pablo JJ; Palecek SP (June 2008). "Engineering tissue from human embryonic stem cells". Journal of Cellular and Molecular Medicine. 12 (3): 709–29. doi:10.1111/j.1582-4934.2008.00228.x. PMC 2670852. PMID 18194458.
- Placzek MR, Chung IM, Macedo HM, et al. (March 2009). "Stem cell bioprocessing: fundamentals and principles". Journal of the Royal Society, Interface. 6 (32): 209–32. doi:10.1098/rsif.2008.0442. PMC 2659585. PMID 19033137.