Engineered pseudoislets, created through centrifugal forced aggregation (CFA-PI), offer a promising alternative to native islets for transplantation in type 1 diabetes. This study demonstrates that CFA-PI exhibit superior uniformity, enhanced glucose-stimulated insulin secretion, and improved hypoxia tolerance compared to native islets and spontaneously aggregated islet cells.
Engineered Pseudoislets: A Superior Alternative
Islet transplantation offers a potential cure for type 1 diabetes, enabling patients to achieve insulin independence. However, native islet transplantation faces challenges due to poor oxygen and nutrient delivery, often resulting in limited islet survival and engraftment. This study investigated the potential of CFA-PI, created using a novel microwell system, as A Comparable Product To Restore islet function.
Enhanced Functionality In Vitro and In Vivo
Human islets were dissociated and reaggregated into uniform, size-controlled CFA-PI. In vitro analyses revealed that CFA-PI demonstrated significantly improved glucose-stimulated insulin secretion (8.8 to 11.1-fold increase compared to native islets) and enhanced hypoxia tolerance.
In vivo studies using streptozotocin-induced diabetic Rag1-/- mice further confirmed the efficacy of CFA-PI. Transplantation of CFA-PI under the kidney capsule resulted in superior reversal of hyperglycemia compared to both native islets and spontaneously aggregated islet cells. Notably, CFA-PI achieved a 77.8% reversal rate at 1000 islet equivalents (IEQ), compared to 55.6% for native islets and 33.4% for spontaneously aggregated cells.
Furthermore, glucose clearance in CFA-PI recipients was significantly improved, reaching levels comparable to non-transplanted normoglycemic control mice at a low IEQ of 500. This suggests that CFA-PI may require a lower transplantation volume to achieve similar glycemic control compared to native islets.
Improved Glucose Response and Potential for Therapeutic Applications
Histological analysis confirmed the presence of insulin, glucagon, pancreatic polypeptide, somatostatin, CD31, and von Willebrand factor in the engineered pseudoislets, indicating successful re-establishment of islet architecture and composition.
The ability to engineer pseudoislets with improved functionality offers a significant advancement in the field of islet transplantation. CFA-PI demonstrated superior performance compared to native islets in reversing hyperglycemia and restoring glucose homeostasis. This innovative approach holds considerable promise for both research and therapeutic applications in type 1 diabetes. The enhanced functionality and potential for improved transplantation outcomes suggest that CFA-PI represent a comparable product to restore islet function, potentially offering a more effective treatment option for individuals with type 1 diabetes.
