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How Islet Autotransplantation Led to the Islet Sheet
December 12th, 2011
When I tell the story of the Islet Sheet these days, I find that I am emphasizing the importance of islet autotransplantation, or autografting. It’s success was the inspiration for the research that led to the Islet Sheet.
The story in brief: The Islet Sheet is a second-generation islet encapsulation device intended to make the benefits of islet transplantation available safely and without the use of toxic immune-suppression drugs. Our goal is to achieve a practical cure as defined by the Juvenile Diabetes Cure Alliance. Already microencapsulation (the first-generation device) has demonstrated some success.
In 2000, the Edmonton Protocol proved that islet transplantation can normalize blood sugar, at the cost of lifetime use of immune-suppression drugs. And before that, the concept of islet transplantation was demonstrated by autografts (any transplant procedure using the patient’s own tissue) of islets to treat chronic pancreatitis. Thus we have known since 1980 that islet transplantation is a metabolic cure, and that the challenge is to transplant islets without immune suppression.
Islet Autotransplantation
The first islet autograft was performed at the University of Minnesota by a team led by Dr. David Sutherland in 1977—coincidentally, the same year I developed type 1 (autoimmune) diabetes. Here is a link to a 1995 publication describing the first 48 patients treated at UM.
The procedure is conceptually simple, but years of research have improved techniques and methods, and the success rate has grown. Chronic pancreatitis can be very painful and may require removal of most or all of the pancreas. If 90% of the pancreas is gone, with it go about 90% of the islets, which usually induces diabetes. The patients do not have islet autoimmunity so are not truly type 1, but metabolically their condition is indistinguishable from autoimmune diabetes. Before 1977, all were treated with insulin injections.
Perhaps the most important results of this research was that the patients most likely to achieve insulin independence were those that received the greatest number of autologous (their own) islets. Figure 6 shows the rate of success by number of islets:
Thirty years later, we now know that the number of islets required for success in islet transplantation is approximately 10,000 islets per kilogram of body weight. This applies to autografts, allografts, and probably to the Islet Sheet.
A Narrow Therapy Can Lead to a Broad Therapy
Surgical treatment of pancreatitis is rare; only a small number of people can be treated with islet autografts. About 400 have been treated at the University of Minnesota since 1977. But it pointed the way.
Just as milkmaids were found to be immune to smallpox because they had already been infected with cowpox, all of the people vaccinated by Edward Jenner were protected from smallpox. The inspiration came from a small, special group: what we learned from that special group eliminated smallpox.
The few hundred people cured by islet autografts inspired years of research leading to the immune-suppression drug cocktails that permitted islet allografts (transplants using tissue from members of the same species; e.g. human islets) to succeed in 2000. The autograft success taught researchers how best to isolate viable islets from the human pancreas. And it taught how many islets are needed for a metabolic cure. The final step was identification of a steroid-free drug protocol by Dr. James Shapiro at the University of Edmonton.
The success of the Edmonton Protocol and islet autografts is our inspiration at the Islet Sheet Project. We want to make the proven benefits of islet transplantation available to all who need insulin to survive and thrive.
