Innovative Approaches to Treating Type 1 Diabetes Addressed in
Beta-Cell Replacement Presentations
Transplanting islet cells from pigs into humans and developing “universal donor” stem cell lines are two innovative approaches being explored for replacing deteriorating beta cells in people with type 1 diabetes, investigators explained during a news briefing and symposium on June 10, 2016, at the American Diabetes Association’s 76th Scientific Sessions® at the Ernest N. Morial Convention Center in New Orleans.
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Transplanting Pig Islet Cells
Pancreatic islet cell transplantation—using islet cells from the pancreas of a deceased human organ donor—has been successfully performed in patients with type 1 diabetes whose blood glucose levels are difficult to control. The procedure can improve blood glucose control, temporarily eliminate the need for insulin injections and improve a patient’s ability to detect hypoglycemia. It is still considered experimental, however, and, due to a shortage of donors, only approximately 1,000 such surgeries have been performed during the last decade.
There is growing evidence to suggest that pig islet cells could provide a viable substitute for human pancreatic islet cell transplantation. David K.C. Cooper, MD, PhD, FRCS, Professor of Surgery, Thomas E. Starzi Transplantation Institute, University of Pittsburgh School of Medicine, reviewed progress to date on treating diabetes with the transplantation of pig pancreatic islet cells that produce insulin, during his symposium presentation, “Pig Islet Xenotransplantation.”
Previous studies have shown successful transplantation of pig islet cells into nonhuman primates (monkeys) with diabetes. “Monkeys with diabetes who received pig islet transplants and received immunosuppressant drug therapy experienced survival rates of more than one year with no need for insulin injections and no major complications,” said Cooper.
He noted, “there have been steady improvements in the results of transplantation of pig islets and organs—for example kidneys—especially from genetically engineered pigs (whose organs and cells are protected to a large extent from the human immune response), into nonhuman primates over the past several years.”
“We are getting closer to initiating trials of pig islet transplantation in human patients with diabetes in whom control of blood sugar is proving difficult,” he said. “With adequate research funding to confirm our recent progress, pig islet transplantation could soon be offered to patients with poorly controlled diabetes.”
“If successful, transplanting pig islet cells into people with type 1 diabetes could help patients maintain normal blood glucose levels without the need for insulin injections, an important benefit for people who experience life-threatening episodes of hypoglycemia following injections,” he explained. “Improved glycemic control from transplantation could also help to prevent later diabetes-related complications such as kidney failure,” he added.
Autologous transplantation, in which a person’s undifferentiated stem cells are removed, grown into a different type of cell and then transplanted back into his or her own body, is another experimental approach for treating degenerative diseases including diabetes. Chad A. Cowan, PhD, Associate Professor in the Department of Stem Cell and Regenerative Biology at Harvard University and Massachusetts General Hospital, an Associate Member of the Broad Institute and a Principal Faculty member of the Harvard Stem Cell Institute where he directs the Diabetes Disease Program and the iPS Cell Core Facility, will share his work in a presentation titled “Universal Donor Stem Cells: Removing the Immune Barrier to Transplantation using Gene Editing.”
“Autologous transplantation has not been considered a viable option since the patient’s immune system would attack the new cells, however, there may be a way around this ‘immune barrier,’” said Cowan. He and his team are currently investigating the possibility of creating “universal donor” pluripotent stem cell (udPSC) lines that could be induced to grow into insulin-producing pancreatic beta cells. “Analogous to the O-negative ‘universal donor’ blood type, udPSCs could be used for all cell-based transplantation therapies in all patients without immune rejection,” he theorized. “Once created, the next step would be to test these udPSC stem cell lines in a humanized mouse model of type 1 diabetes,” Cowan said.
“If successful, our proposed work could have an enormous impact on regenerative medicine. It could lead the way to rigorously tested universal donor stem cells that could be grown and differentiated into very large numbers of cells, made widely available to all medical institutions and used on demand to treat patients suffering from type 1 diabetes and a variety of degenerative illnesses,” Cowan concluded.