Enhancing the Functionality of Immunoisolated Human SC-βeta Cell Clusters through Prior Resizing

The transplantation of immunoisolated stem cell derived beta cell clusters (SC-β) has the potential to restore physiological glycemic control in patients with type I diabetes. This strategy is attractive as it uses a renewable β-cell source without the need for systemic immune suppression. SC-β cells have been shown to reverse diabetes in immune compromised mice when transplanted as ≈300 µm diameter clusters into sites where they can become revascularized. However, immunoisolated SC-β clusters are not directly revascularized and rely on slower diffusion of nutrients through a membrane. It is hypothesized that smaller SC-β cell clusters (≈150 µm diameter), more similar to islets, will perform better within immunoisolation devices due to enhanced mass transport. To test this, SC-β cells are resized into small clusters, encapsulated in alginate spheres, and coated with a biocompatible A10 polycation coating that resists fibrosis. After transplantation into diabetic immune competent C57BL/6 mice, the "resized" SC-β cells plus the A10 biocompatible polycation coating induced long-term euglycemia in the mice (6 months). After retrieval, the resized A10 SC-β cells exhibited the least amount of fibrosis and enhanced markers of β-cell maturation. The utilization of small SC-β cell clusters within immunoprotection devices may improve clinical translation in the future.