1808-PUB: Effective and Durable Stem-Cell-Enabled Therapy of Autoimmune T1DM in Rodents and Dogs Provides the Scientific Basis for the First-in-Human Trial Using I.P. Administered “Neo-Islets,” 3-D Organoids of Allogeneic Islet, and Mesenchymal Stromal Cells—The Omentum Becomes the New Endocrine Pancreas without the Need for Antirejection Drugs

Two initial reports from Clinical Trials with cell-based interventions for the urgently needed therapy of T1DM show: (a) Open, s.c.-placed encapsulation devices containing insulin-producing progenitor cells that require anti-rejection drugs have failed to adequately improve glycemic control. (b) The intraportal administration of stem cell-derived insulin-producing cells, requiring anti-rejection drugs, has shown promising results in 2 or 3 subjects. However, the inability to retrieve these cells and the need for anti-rejection drugs remain a concern. Our approach harnesses the immune-modulating and -isolating, anti-inflammatory, angiogenic, anti-apoptotic and other trophic actions of Mesenchymal Stromal Cells (MSCs). First, we demonstrated that allogeneic Neo-islets (NIs), islet-sized organoids composed of equal numbers of MSCs and culture expanded Islet Cells do, when given i.p., omentally engraft, redifferentiate, re-express all islet hormones and permanently restore euglycemia in auto-immune diabetic NOD mice, i.e., without encapsulation devices or antirejection drugs. The omentum becomes the new endocrine pancreas. Second, i.p. therapy of spontaneously diabetic pet dogs with allogeneic canine NIs significantly improved glycemia and insulin needs (> 3 years), and this without immune response (abstract this meeting). Third, human NIs permanently correct streptozotocin-induced diabetes in NOD/SCID mice. Removal of the omentally-engrafted NIs promptly restores the diabetic state. No long-term complications of the NI therapy have been observed. Based on this body of evidence, a successful Pre-IND meeting with the FDA was held and final Proof-of-Concept studies that are expected to lead IND approval are ongoing.