AT THE ADA ANNUAL SCIENTIFIC SESSIONS

NEW ORLEANS (FRONTLINE MEDICAL NEWS) — Two researchers shared innovative ideas at the annual scientific sessions of the American Diabetes Association for tapping virtually unlimited supplies of islet cells with less risk of an immune reaction.

Transplanting pancreatic islet stem cells from deceased donors into patients with type 1 diabetes has long been known to be an effective way of improve blood-glucose levels and temporarily eliminate the need for insulin injections, but getting an adequate supply of islet cells to treat the 1 million-2 million Americans with Type 1 diabetes, not to mention the risk of rejection and the need for long-term immunosuppressive therapy, makes this approach challenging.

At the University of Pittsburgh, investigators have developed a way to harvest islet cells from genetically engineered pigs and implant them into monkeys, while at the Harvard Stem Cell Institute in Boston, researchers have used gene editing to grow islet cells from blood cells.

“Human islet cells are in very scarce supply and will never solve the problem of diabetes,” said Dr. David K.C. Cooper, professor at the Thomas E. Starzi Transplantation Institute at the University of Pittsburgh. But growing evidence has shown that islet cells harvested from pigs could provide a viable source.

The challenge with stem cells from deceased human donors is that they require long term immunosuppression therapy to prevent the host body from rejecting them. When Dr. Cooper and his team injected islet cells from genetically engineered pigs into the stomachs of monkeys, they found the monkeys were able to maintain blood glucose control for about a year while on “fairly basic immunosuppressive therapy.” Dr. Cooper explained that the immunosuppressive regimen is a nonthrombogenic, monoclonal antibody not yet approved by the Food and Drug Administration. He noted that work at the Seoul National University in Korea has found similar results in monkeys out to 2 years.

The concept involves raising genetically engineered pigs in a biosecure facility, of which there are “two or three” in the United States, to ensure the cells are infection free. “The pig will be the answer to our problems,” Dr. Cooper said.

At Harvard, meanwhile, researchers are developing a way to produce pluripotent stem cells using an individual’s own blood cells that function like embryonic stem cells, but can multiply in a virtually unlimited fashion, Chad Cowan, PhD, reported. The challenge with using stem cells produced from an individual’s own cells has been the “immune barrier” – that is, the person’s immune system would attack the new cells.

However, Dr. Cowan and his team have found a way around this so-called “immune barrier” by producing “universal donor” pluripotent stem cell lines.

“You have an unlimited supply of cells,” Dr. Cowan said. “The key, though, is to teach these cells to do something, and because they come from a very early stage in development, they have the ability to become any of the adult cells in the human body. Our mission has been to teach them to become insulin-producing beta cells.”

The idea is to grow an “off-the-shelf, quality-controlled” product that can be produced in large numbers. By editing the genes, the researchers aim to reduce the immunogenicity of these cells and induce tolerance.

The work is some time away from human trials. “Once created, the next step would be to test these universal donor pluripotent stem cell lines in a humanized mouse model of type 1 diabetes,” Dr. Cowan said.

This type of gene editing also could have implications beyond diabetes, Dr. Cowan said. “If successful, our proposed work could have an enormous impact on regenerative medicine,” he said. “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,” including Parkinson’s disease.

Dr. Cowan and Dr. Cooper reported having no financial disclosures.

cenews@frontlinemedcom.com

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