Islet Therapy Gains Ground
Researchers have found better ways to use transplanted islet cells to help people with T1 produce insulin again.
As a rule, researchers are a cautious bunch who aren’t given to excessive optimism. That makes the hopeful tone of Dr. Peter Stock all the more persuasive when he talks about advances in islet therapy. As co-director of the Clinical Islet Transplant Program at the University of California, San Francisco (UCSF), Dr. Stock is one of the scientists on the frontline of trying to make islet therapy a viable, everyday option for people with Type 1 diabetes.
The therapy, which transplants healthy, insulin-producing islet cells into the body of someone with diabetes, has always held great promise, but it has come with significant hurdles. Chief among these are that the body’s immune system kills off many of the transplanted islet cells, and many islet cells die during transplantation. Now, Dr. Stock believes, medical advances are making islet therapy much more possible.
“We’ve been saying islet therapy is ‘right around the corner’ for quite a while, but now it really seems to be true,” he says.
You can be forgiven for needing proof if you’ve heard this before, but Dr. Stock seems in a good position to know. He and other researchers believe islet cell transplantation is poised to eventually replace whole pancreas transplants and insulin injections as the dominant therapy in treating Type 1 diabetes. The improving statistics of the success rate of islet therapy kindle hope for the therapy. Before 2005, only 10% of all islet transplant patients were able to maintain insulin independence after 5 years. Today, that figure is 50% – similar to the 5-year success rate of pancreas transplants. At UCSF, physicians have gone beyond that, says Dr. Qizhi Tang, director of UCSF’s Transplantation Research Laboratory.
“By carefully selecting immunosuppressive drugs, we have achieved 80% insulin independence at 5 years post-islet transplant,” Dr. Tang says.
Hurdles to Overcome
The biggest hurdle to widespread islet transplant therapy now might be cost. The procedure’s current status is still listed as “experimental” and not covered by health insurance plans. In the U.S., estimated costs for an infusion of islets from a single donor can total over $80,000 – and double if further infusions are required, says Dr. Stock.
All islet transplants currently done in the U.S. to date have been supported by research funding. The National Institutes of Health recently concluded a multi-center U.S. trial, which will determine whether islet transplantation will become an FDA-approved procedure. Hopefully this will happen within the next 2 years and lead to insurance coverage, Dr. Stock says. As is often the case with newer forms of T1 therapy, the U.S. health insurance system is slower to adopt this therapy than health insurance systems in other countries. The countries now excelling in islet therapy, including some European countries and Canada, all have universal health care, Dr. Stock says.
There is still a lot of work that needs to be done before islet therapy can be as successful as insulin injection therapy. Dr. Tang sees 2 critical areas in need of improvement. The first is a perpetual shortage of islet donors, since it often takes two donors to get one recipient insulin independent, reports Dr. Tang. One reason for the 2-to-1 ratio is that only 50% of the islet cells are extricated alive from the pancreas of donors and another 40% die shortly after transplant.
“Reducing this die-off rate would make much better use of existing donors,” Dr. Tang says.
A way to overcome this barrier would be to use stem cells to create more islet cells. Stem cells appear to be the wave of the future for islet therapy, but scientists need to learn more about how to harness them to make islet cells, Dr. Tang says.
“Currently, they don’t function for the first 3 months. And because they still have stem cell properties, they don’t all become islet cells,” she says.
Another challenge scientists ponder is how to encapsulate the transplanted islet cells to shield them from the body’s immune system. Currently, islet transplant recipients must commit to life-long immunosuppression — a deal-breaker for many patients. Finding a way to shield new islets requires a delicate balancing act, says Dr. Tang.
“Encapsulation materials need to be robust enough so they don’t break, but not so thick that the islet cells’ ability to sense glucose levels is impaired. Glucose and other nutrients need to get in, and insulin needs to come out freely,” she says.
Perhaps the best way around these complications is to keep more islets alive during the transplant process. Dr. Tang’s lab is studying ways to prevent the 90% islet cell death during transplantation—including preparing islet cells to survive low oxygen conditions and studying the lack of nutrients that may be contributing to islet cell death.
Another focus of study at UCSF is making islet therapy more user-friendly for the immune system. One problem with initial islet trials was that the immunosuppressive agents needed to make the therapy work often damaged the kidneys. Dr. Stock and Dr. Tang are studying ways to use an antibody immunosuppression technique which deactivates the T cells that cause transplant rejection. UCSF performs some 500 major organ transplants a year, and the novel strategies used to prevent solid organ transplant rejection can also be applied to islet transplantation.
“We have the whole package in one place,” says Dr. Tang.
Islet therapy is an evolving field of study, and each new advance brings with it new questions. For example, scientists are just beginning to ponder whether porcine islets can be transplanted successfully to humans, and stem cell techniques are still in their infancy. But islet therapy has now become a scientifically viable option, if not always an economically possible one, and researchers like Dr. Stock and Dr. Tang only see room for improvement.
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