In the first step toward animal-to-human transplants of insulin-producing cells for people with type 1 diabetes, Northwestern Medicine® scientists have successfully transplanted islets, the cells that produce insulin, from one species to another. And the islets survived without immunosuppressive drugs.
Northwestern scientists developed a new method that prevented rejection of the islets, a huge problem in transplants between species, called xenotransplantation.
“This is the first time that an interspecies transplant of islet cells has been achieved for an indefinite period of time without the use of immunosuppressive drugs,” said study co-senior author Stephen Miller. “It’s a big step forward.”
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Ref: Transient B Cell Depletion Combined with Apoptotic Donor Splenocytes Induces Xeno-specific T and B cell Tolerance to Islet Xenografts. Diabetes (30 May 2013) | DOI: 10.2337/db12-1678
Peritransplant infusion of apoptotic donor splenocytes cross-linked with ethylene carbodiimide (ECDI-SPs) has been demonstrated to effectively induce allogeneic donor-specific tolerance. The objective of the current study is to determine the effectiveness and additional requirements for tolerance induction for xenogeneic islet transplantation using donor ECDI-SPs. In a rat-to-mouse xenogeneic islet transplant model, we show that rat ECDI-SPs alone significantly prolonged islet xenograft survival, but failed to induce tolerance. In contrast to allogeneic donor ECDI-SPs, xenogeneic donor ECDI-SPs induced production of xenodonor-specific antibodies partially responsible for the eventual islet xenograft rejection. Consequently, depletion of B cells prior to infusions of rat ECDI-SPs effectively prevented such antibody production and led to the indefinite survival of rat islet xenografts. In addition to controlling antibody responses, transient B cell depletion combined with ECDI-SPs synergistically suppressed xenodonor-specific T cell priming as well as memory T cell generation. Reciprocally, after initial depletion, the recovered B cells in long-term tolerized mice exhibited xenodonor-specific hypo-responsiveness. We conclude that transient B cell depletion combined with donor ECDI-SPs is a robust strategy for induction of xenodonor-specific T and B cell tolerance. This combinatorial therapy may be a promising strategy for tolerance induction for clinical xenogeneic islet transplantation.