Therapeutic immune tolerant human islet-like organoids (HILOs) for Type 1 Diabetes

Insulin-producing pancreatic islets are a promising therapy for type 1 and severe type 2 diabetic patients that require insulin injections.  However, many challenges remain before this goal can be reached.  We have been able to generate human islet-like organoids (HILOs) from human stem cells and identify mechanisms that promote their maturation, transforming them into glucose-responsive insulin-secreting cells.  We demonstrate that upon transplantation into diabetic mice, our organoids can rescue the diabetic phenotype and restore glucose balance.  In addition, we have found a method whereby we can activate an immune “shield” to protect our organoids from attack by the host immune system.  In immune-competent mice, this has allowed our HILOs to prevent hyperglycemia for over 50 days.  Our ability to generate glucose-responsive islet-like organoids that are able to avoid immune detection provides a promising alternative to cadaveric and device-dependent therapies in the treatment of diabetes.