An Ultra filtrate perfusion bio artificial pancreas for high-density islet replacement without immunosuppression

? DESCRIPTION (provided by applicant): The Cell-SafeTM is a fundamentally new approach in replacement of dysfunctional insulin-producing cells in patients with diabetes, by transplantation of new islets in a three-dimensional scaffold embedded in a highly compatible bioengineered perfusion system that continuously supplies tissue fluid (blood ultrafiltrate), so that the cells ae protected from immune rejection but have optimal exchange of oxygen and nutrients. This compact device is totally implanted in the subcutaneous space and the unique design facilitates loading, reloading, and biopsy of cell products using simple needle access through the skin. The pump-controlled ultrafiltrate perfusion system supplies oxygen, nutrients, and flushes metabolic waste. Thanks to the immunoisolation environment survival of transplanted islets can be achieved in complete absence of immunosuppression. This approach could solve the issues in islet transplantation, namely the complications of immunosuppressive medication and scarcity of human donor pancreases, which issues have severely limited islet cell transplantation to a select group of patients who suffer from insufficient control of their blood sugar level and hence are at risk for developing diabetes complications. Control of blood sugar levels is restored in most patients who receive an allograft transplant, but unfortunately long-term allograft survival rates are low and the most patients will eventually require retransplant to continue benefiting from the therapy. Success of the Cell-SafeTM device has an immediate implication for human islet allotransplantation, but also would facilitate `unlimited' cell sources like xenogeneic porcie islets or stem cell-derived insulin-producing cells. Taken together this technology presents a major paradigm shift in ?-cell replacement therapy. The Phase 1 project will evaluate the capacity of the device, islet reloading schemes, and characterize factors in blood ultrafiltrate tht support islet function and survival that was demonstrated in preliminary studies. At the same time, in vitro stress testing of the device will be performed to prepare for clinical manufacturing The Phase 2 will focus on preclinical pivotal trials addressing safety/tolerability and efficacy, intended to support regulatory approval of this device with the final aim of meeting the tremendous clinical need for safe, effective, and durable islet replacement that also enables expanded accessibility of this therapy in diabetes patients.