Camillo Ricordi, MD, FNAI, discusses some of the potential risks faced by patients with type 1 diabetes who undergo islet transplantation.
An unlimited source of stem cell–derived islets and new immunomodulatory strategies could represent the next quantum leap in the field of cell therapy, said Camillo Ricordi, MD, FNAI, a professor and director of the Diabetes Research Institute and Cell Transplant Center at the University of Miami, Florida.
What risks accompany islet transplantation for type 1 diabetes?
The risks of islet transplantation in the past have been typically the potential bleeding from the site of puncture of the liver. In the old days in unpurified transplantation, islets were transplanted, you could have problems with the thrombosis of the portal vein in the liver. But this recently has been a risk that has been virtually eliminated and also modern technology for transplant with interventional radiology, obliterating the track or infuse the islets, have virtually eliminated the risk of bleeding, which still remains maybe 5% or less.
But that bleeding, as I said, control does not require typically transfusion or anything, you may have a little hematoma at the site of the puncture of the liver. The other risk associated with islet transplantation are the traditional risks associated with the chronic use of antirejection drugs. So that immunosuppression is associated with a higher risk of infection or even tumors. But this, surprisingly, has not been associated with an increased risk of mortality or risk of death in subject with islet transplants and immunosuppression. That is actually less compared to subjects that don't take a transplant that they've just been screened in the absence of immunosuppression. So this is very promising.
Also, in view of the fact that the modern, new trials will replace immunosuppression with these immunomodulatory substances that are not associated with the same risk of traditional immunosuppression. Moving forward, this new trial that was approved in Canada and we're waiting for approval in the United States by Eledon Pharmaceuticals is an anti-CD40 ligand that is a costimulatory blocking molecule that will replace Prograf (tacrolimus) immunosuppressant. And this will be a major step forward, as we can see already from preclinical studies where the islets produce 3 times more C-peptide, more insulin, in the absence of these toxic antirejection drugs like Prograf that are associated with diabetes, even in subjects that have not diabetes to begin with, the so-called transplant diabetes.
I think that moving forward, replacing these drugs that are diabetogenic, besides this side effect of immunosuppression, with immunomodulatory strategies that are not, that don't have side effects, and allow the islets to survive and function will fare much better, will be the next quantum leap in the field. The next quantum leap will be also this new trial that we are starting, as we're speaking, with the stem cell–derived islet cells that may eliminate the shortage of organs. As we know, in United States over 11,000 patients die every year for lack of organs that can be transplanted. The ability to have stem cell–derived islets in an unlimited fashion will be tremendous because otherwise based on human organ donation, it would become a lottery. If everybody wants an islet transplant, who will actually be able to benefit? So I think that the combination between an unlimited source of stem cell–derived islets and new immunomodulatory strategies like the anti-CD40 ligand costimulatory blockade could become and represent the next quantum leap in the field of cell therapy and biologic replacement for treatment of diabetes: not just type 1 diabetes, but also insulin-requiring type 2 diabetes.