Allogeneic "Neo-lslets," Organoids Composed of Cultured Pancreatic Islet and Mesenchymal Stromal Cells from Diverse Donors, Afford a Marked Increase in the Global Availability of a Curative, Novel, Anti-Rejection-Drug-Independent Biotherapy of T1DM

The scarcity of suitable pancreas/islet donors, the life-long need for potentially toxic anti-rejection drugs for transplants and certain biotherapies, and failure of some immune-isolating encapsulation devices collectively warrant the urgent development of novel therapies for T1DM that significantly expand the donor pool without reliance on anti-rejection drugs. Allogeneic, i.p.-administered “Neo-Islets” (NIs) are potentially such a therapy. We previously reported that the use of NIs reestablished permanent normoglycemia in autoimmune diabetic NOD mice without immunosuppression. Our FDA-guided pilot study (INAD 012-0776) in insulin dependent, spontaneously diabetic pet dogs showed similar, durable responses, also without immunosuppression. Scoring systems have improved allotransplantation outcomes while their use may actually waste potentially valuable cells for novel diabetes therapies such as NIs. In preparation for a Phase 1 clinical trial with NIs, we examined whether human “non-clinical grade” islets from diverse, nondiabetic human and canine donors (n=6-8 each) could be processed to generate fully functioning NIs. Islet gene expression profiles (insulin, others) in both species closely correlate with population doublings and GSIS responses. Human-NIs establish normoglycemia in STZ diabetic NOD/SCID mice. Based on these results, an estimated 600 therapeutic doses can be generated from a single islet donor. Conclusion: human-NIs created from diverse, “non-clinical grade” donors have the potential to greatly expand patient access to this curative therapy, facilitated by biotherapy-specific adjustments in the current scoring systems. Disclosure C. Westenfelder: Consultant; Self; SymbioCellTech. S. S. Chowdhury: Employee; Self; SymbioCellTech. A. Gooch: Employee; Self; SymbioCellTech.