Regenerative medicine

Regenerative medicine is the "process of replacing or regenerating human cells, tissues or organs to restore or 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. Depending on the source of cells, it can potentially solve the problem of organ transplant rejection if the organ's cells are derived from the patient's own tissue or cells.

Widely attributed to having first been coined by William Haseltine (founder of Human Genome Sciences), the term "Regenerative Medicine" was first found 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 cells. Examples include the injection of stem cells or progenitor cells (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).

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. For example, in abdominal wall reconstruction (like inguinal hernia repair), biologic meshes are being used with some success.

Pioneers
At the Wake Forest Institute for Regenerative Medicine, in North Carolina, Dr. Anthony Atala 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, 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. As of 2011, this new technology is being employed by the military to U.S. war veterans in Texas, as well as to some civilian patients. Nicknamed "pixie-dust" the powdered extracellular matrix is being used with great success to regenerate tissue lost and damaged due to traumatic injuries. For example, a 19-year old male patient who lost a significant amount of tissue on his heel after a fall from a cliff received two applications of the extracellular matrix powder at Kaiser Hospital in Roseville, California. His heel successfully regenerated, avoiding the necessity of bone and skin grafts, as well as other reconstructive surgery.

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.

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,. 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.

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.

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.