HomeMedical SpecialtiesDiseasesFuture directions in cell transplantation for Type I Diabetes

Future directions in cell transplantation for Type I Diabetes

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Type I Diabetes is a chronic condition caused by a loss of insulin-secreting beta cells. These cells are normally located within the islets of the pancreas but Dr. James Shapiro at the University of Alberta found a second home for them in the liver. In 2000, Shapiro published his landmark Edmonton Protocol in the New England Journal of Medicine when he conducted islet transplantations in seven patients with Type I Diabetes. Shapiro’s team has performed over 400 procedures in more than 200 patients, providing one of the most revolutionary treatments for diabetes since Banting’s discovery of insulin in 1921.

The team works with donated pancreata, separating the islets from the organ tissue and transplanting them into the patient’s liver. Within a few weeks the beta cells are able to make and secrete insulin, reducing or eliminating the patient’s need for injections. Most patients need two separate transplant procedures, requiring at least two donated organs.

MORE: THE DIABETES EPIDEMIC

Islet transplantation is recommended for diabetics with frequent or severe episodes of hypoglycemia. Most patients remain insulin independent for about two-and-a-half years following transplant with only 15-20 per cent maintaining this status at the five-year mark. The remaining 80 per cent of patients still benefit from lower doses of insulin to maintain stable blood sugars and freedom from hypoglycemia. All patients require immunosuppressive therapy as long as the islet transplant is functioning.  Research continues to work on improving long-term islet graft survival and function by further refinement of immunosuppressant therapy, alternative transplantation sites and finding other sources of beta cells.

The need for multiple donor pancreata per patient coupled with low rates of organ donation has lead to the search for other sources of the insulin-secreting beta cells. Advances in embryonic and induced pluripotent stem cell biology provide the potential to generate these cells in a petri dish. Embryonic stem cells are sourced from embryos generated by in vitro fertilization and donated to research and are unique in that they can become any cell type in the body and repeatedly self-renew. Induced pluripotent stem cells are adult cells (such as blood or skin cells) altered by genetic technology so they function like embryonic stem cells.

No laboratory has been able to generate bona fide human beta cells. However, a recent discovery has shown that a key cell (beta cell progenitor) can be developed from human embryonic stem cells. When these progenitor cells are transplanted into mice, they can create functional beta cells, meaning they are sensitive to glucose levels and release insulin accordingly. US-based companies are in the process of launching clinical trials to test these cells in humans. Dr. Shapiro has been working with ViaCyte, Inc., a regenerative medicine company based in San Diego, for the last ten years. Together they are ready to start a Phase 1 Clinical Trial to test the safety and efficacy of the cells. They will also evaluate a special device, Encaptra, which assists with the delivery of the cells and protects them from attack by the patient’s immune system.

 MORE: TAKING ACTION AGAINST CHILDHOOD OBESITY

Shapiro indicates there are some challenges with this therapy, “Is it safe and effective? How much will the therapy cost? Will the cells last once they’ve been transplanted? These are the questions we are asking right now. This clinical trial is an incredible milestone for diabetes research and it’s exciting that it’s happening right here in Canada.”

Dr. M. Cristina Nostro, Scientist at University Health Network, and Harry Rosen Chair in Diabetes Regenerative Medicine Research at the McEwen Centre for Regenerative Medicine, agrees protecting the cells from attack by the immune system is a challenge.

“As cell therapy for Type I Diabetes is moving to the clinic, scientists and engineers around the world are working towards the generation of devices that will not only protect the beta cells from the immune system but will also provide the right support for the growth and survival of the transplanted cells,” says Nostro.

Nostro is working towards the development of an efficient method to generate the beta cell progenitors from either embryonic or induced pluripotent stem cells. Nostro indicates that, “A method that could be applied to any pluripotent stem cell line will allow for more universal applications.”

These are exciting discoveries that give hope to diabetics around the world but continued patience and caution is necessary, “Human embryonic stem cell-derived cells are already in clinical trials for the treatment of macular degeneration. I look forward to seeing the start of the first trial using these cells for the treatment of Type I Diabetes as it will revolutionize the way we treat and think of this disease,” says Nostro, a member of the Ontario Stem Cell Initiative.

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