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

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Abstract
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.
Funding Information
  • National Institutes of Health (EB031992)
  • Agentúra na Podporu Výskumu a Vývoja (APVV‐18‐0480, APVV‐22‐0565)
  • National Cancer Institute (P30‐CA14051)
  • Juvenile Diabetes Research Foundation International (2‐SRA‐2019‐714, ‐S‐B, 2‐SRA‐2018‐521‐S‐B)

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