Regenerative medicine
Encyclopedia
establish normal function". This field holds the promise of regenerating damaged tissues and organs in the body by replacing damaged tissue and/or by stimulating the body's own repair mechanisms to heal previously irreparable tissues or organs. Regenerative medicine also empowers scientists to grow tissues and organs in the laboratory and safely implant them when the body cannot heal itself. Importantly, regenerative medicine has the potential to solve the problem of the shortage of organs available for donation compared to the number of patients that require life-saving organ transplantation, as well as solve the problem of organ transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
rejection, since the organ's cells will match that of the patient.
Widely attributed (incorrectly as it turns out) to having first been coined by William Haseltine (founder of Human Genome Sciences
Human Genome Sciences
Human Genome Sciences is a biopharmaceutical corporation founded in 1992. It uses the human DNA sequence to develop protein and antibody drugs. As of 2008, it has drugs under development to treat such diseases as hepatitis C, systemic lupus erythmatosis, anthrax disease, cancer, rheumatoid...
). From the work of Michael Lysaght (Brown University), his team "first found the term 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 such paragraph had ‘‘Regenerative Medicine’’ as a bold print title and went on to state, ‘‘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.’’
Regenerative Medicine refers to a group of biomedical approaches to clinical therapies that may involve the use of stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s. Examples include the injection of stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s or progenitor cell
Progenitor cell
A progenitor cell is a biological cell that, like a stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its "target" cell...
s (cell therapies
Cell therapy
Cell therapy describes the process of introducing new cells into a tissue in order to treat a disease. Cell therapies often focus on the treatment of hereditary diseases, with or without the addition of gene therapy...
); the induction of regeneration
Regeneration (biology)
In biology, regeneration is the process of renewal, restoration, and growth that makes genomes, cells, organs, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. At its most...
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
Tissue engineering
Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physio-chemical factors to improve or replace biological functions...
).
A form of regenerative medicine that recently made it into clinical practice, is the use of heparan sulfate analogues on (chronic) wound healing. Heparan sulfate analogues replace degraded heparan sulfate at the wound site. They assist the damaged tissue to heal itself by repositioning growth factors and cytokines back into the damaged extracellular matrix.
Pioneers
At the Wake Forest Institute for Regenerative MedicineWake Forest Institute for Regenerative Medicine
Wake Forest Institute for Regenerative Medicine is a research institute affiliated with the Wake Forest School of Medicine and located at Winston-Salem, North Carolina, United States...
, in North Carolina, Dr. Anthony Atala
Anthony Atala
Anthony Atala, M.D., is the W.H. Boyce Professor and Director of the Wake Forest Institute for Regenerative Medicine, and Chair of the Department of Urology at the Wake Forest University School of Medicine in North Carolina...
and his colleagues have successfully extracted muscle and bladder cells from several patients' bodies, cultivated these cells in petri dishes, and then layered the cells in three-dimensional molds that resembled the shapes of the bladders. Within weeks, the cells in the molds began functioning as regular bladders which were then implanted back into the patients' bodies. The team is currently working on re-growing over 22 other different organs including the Liver, Heart, Kidneys and Testicles.
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
University of Pittsburgh
The University of Pittsburgh, commonly referred to as Pitt, is a state-related research university located in Pittsburgh, Pennsylvania, United States. Founded as Pittsburgh Academy in 1787 on what was then the American frontier, Pitt is one of the oldest continuously chartered institutions of...
, has developed a process which involves 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 cellular 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. However, Ben Goldacre
Ben Goldacre
Ben Michael Goldacre born 1974 is a British science writer, doctor and psychiatrist. He is the author of The Guardian newspaper's weekly Bad Science column and a book of the same title, published by Fourth Estate in September 2008....
has described this as "the missing finger that never was", claiming that fingertips regrow and quoted Simon Kay, professor of hand surgery at the University of Leeds, who from the picture provided by Goldacre described the case as seemingly "an ordinary fingertip injury with quite unremarkable healing" and as "junk science".
In June 2008, at the Hospital Clínic de Barcelona, Professor Paolo Macchiarini
Paolo Macchiarini
Paolo Macchiarini, M.D., Ph.D. is head and chairman of the Hospital Clínic de Barcelona, University of Barcelona in Barcelona, Spain, as well as professor of surgery at the University of Barcelona in Spain, and at the Hannover Medical School in Hannover, Germany.Dr. Macchiarini completed his...
and his team, of the University of Barcelona
University of Barcelona
The University of Barcelona is a public university located in the city of Barcelona, Catalonia in Spain. It is a member of the Coimbra Group, LERU, European University Association, Mediterranean Universities Union, International Research Universities Network and Vives Network...
, 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 chondrocyte
Chondrocyte
Chondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans...
s, 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.
Cord blood and Regenerative Medicine
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 and Type 1 Diabetes is already being studied in humans, and earlier stage research is being conducted for treatments of stroke, and hearing loss.
Current estimates indicate that approximately 1 in 3 Americans could benefit from regenerative medicine, and children whose cord blood stem cells are available for their own potential use could be among the first to benefit from new therapies as they become available. With autologous (the person’s own) cells, there is no risk of the immune system rejecting the cells, so physicians and researchers are only performing these potential cord blood therapies on children who have their own stem cells available.
Researchers are exploring the use of cord blood stem cells in the following regenerative medicine applications:
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.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.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. 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.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.
Another report published encouraging results in 2 toddlers with cerebral palsy where autologous cord blood infusion was combined with G-CSF.
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.
Heparan Sulfate Analogues
Heparan sulfates glycosylaminoglycans bind to the heparan sulfate binding domain of matrix proteins such as collagens and fibronectin on the extracellular matrix. Heparan sulfate consist of a chain of subunits of 85kD which is negatively charged and can therefore interact with the slightly positively charged basic amino acids of growth factors and cytokines, protecting and holding them in the process. In any wound area heparan sulfates are degraded by glycanases and heparanases. This disrupts the normal tissue homeostasis because the different growth factors and cytokines cannot be held and protected by the heparan sulfate.Heparan sulfate analogue is a synthetic heparan sulfate mimetic. Due to a different coupling of subunits it is resistant to enzymatic degradation: the β2-4 carbon-carbon binding of the subunits of heperan sulfate is prone to enzymatic cleavage whereas the α1-6 carbon-carbon binding of the subunits of heparan sulfate analogues are resistant to cleavage by all known glycanases and heparanases .
Heparan sulfate analogues have shown significant improvement on different kind of wounds in pre-clinical research. Animal research has shown that heparan sulfate analogues help the wounds heal but retain the normal tissue structure and prevent scarring.
See also
- Artificial organArtificial organAn artificial organ is a man-made device that is implanted or integrated into a human to replace a natural organ, for the purpose of restoring a specific function or a group of related functions so the patient may return to as normal a life as possible...
- AxolotlAxolotlThe axolotl , Ambystoma mexicanum, is a neotenic salamander, closely related to the Tiger Salamander. Larvae of this species fail to undergo metamorphosis, so the adults remain aquatic and gilled. It is also called ajolote...
- BiomedicineBiomedicineBiomedicine is a branch of medical science that applies biological and other natural-science principles to clinical practice,. Biomedicine, i.e. medical research, involves the study of physiological processes with methods from biology, chemistry and physics. Approaches range from understanding...
- Regeneration (biology)Regeneration (biology)In biology, regeneration is the process of renewal, restoration, and growth that makes genomes, cells, organs, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. At its most...
- Rejuvenation (aging)Rejuvenation (aging)Rejuvenation is the hypothetical reversal of the aging process.Rejuvenation is distinct from life extension. Life extension strategies often study the causes of aging and try to oppose those causes in order to slow aging...
- Stem Cell TreatmentsStem cell treatmentsStem cell treatments are a type of intervention strategy that introduces new cells into damaged tissue in order to treat disease or injury. Many medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering...
- TERMISTissue Engineering and Regenerative Medicine International SocietyTissue Engineering and Regenerative Medicine International Society is an international learned society. Its goal is the worldwide advancement of both the science and technology of tissue engineering and regenerative medicine.- History and structure :...
- Heparan sulfate analogueHeparan sulfate analogueHeparan sulfate analogues are polymers engineered to mimic several properties of heparan sulfates. They can be constituted with a backbone of polysaccharides, such as poly glucose or glucuronates or a polyester such as co polymers of lactic or malic acid to which sulfates, sulfonate or...
External links
Less technical further reading- Regenerative Medicine, 2006 report, US National Institutes of Health
- Center for Regenerative Medicine, More on history, healing potential and research activities on autologus stem cells technologies in regenerative medicine.
More technical further reading
Scientific Journals