1508-P: The Therapy of Type 1 Diabetes Mellitus with Neo-islets, 3-D Organoids of Mesenchymal Stromal and Islet Cells, Has the Capacity to Compensate for the Very Low Procurement Rate of Pancreata and Islets and This without the Need for Antirejection Drugs

The current number of patients with T1DM in the US is ~1.8 million, and globally ~ 58 million. In the last 10 yrs only ~ 4,400 islet allotransplants have been performed globally, while the number of deceased Organ Donors per yr in the US is ~ 15,000 and globally ~ 36,000. This demonstrates that inadequate numbers of pancreata and islets are harvested, particularly for potentially curative islet transplants. To address this organ shortage for the biotherapy of T1DM, we have engineered “Neo-islets” (NIs), islet-sized cell clusters that are composed in a 1:1 ratio of allogeneic Mesenchymal Stromal (MSCs) and culture expanded islet cells (ICs). Importantly, islets that do not meet the quality scores for clinical transplants and that are ordinarily discarded can be used to generate the needed ICs in NIs, i.e., from one such islet donor ~ 270 therapeutic NIs doses can be produced. In contrast, islet transplants require often more than one islet donor and often repeatedly. The MSC component in NIs provides durable and local allo- and auto-immune isolation that eliminates the need for anti-rejection drugs, together with powerful anti-inflammatory, proangiogenic, and anti-apoptotic actions in autoimmune, T1DM NOD mice and dogs. NIs are administered i.p. under ultrasound guidance to sedated recipients, a minimally invasive, ~15 min procedure. NIs spontaneously engraft in the recipient’s omentum from where they physiologically deliver insulin and all other islet hormones intraportally as the pancreas does. They can be retrieved if needed, which is not possible with intraportal islet or other cell-based transplants. After a successful Pre-IND meeting with the FDA, we received approval for the conduct of the required IND-enabling POC study. With receipt of the respective IND, we will carry out our Phase I/II Clinical Trial at three collaborating institutions in California.