Enhancing pancreatic β-cell viability and longevity through novel microencapsulation strategies and stromal cell support

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Type 1 diabetes (T1D) is a disease in which the β-cells in the pancreas are destroyed by autoimmune attacks. Islet transplantation (a procedure where insulin-producing cells from a donor are transferred to someone with type 1 diabetes) is proposed as an effective cure for Type 1 diabetes because it regulates glucose levels from minute to minute.

Despite the potential benefits, islet transplantation faces challenges that limit its widespread application. One of the main obstacles is the need for lifelong immunosuppression to prevent graft rejection. Immunoisolation of islets, by encapsulating the tissue in semi-permeable membranes, circumvents the need for immunosuppression. However, despite the success in treating Type 1 diabetes demonstrated by encapsulated cells, graft survival was typically limited to a few months in most studies. This limited its clinical application.

Therefore, a new composite microcapsule has been adopted to enhance the survival and function of immuno-isolated islets. Multiple approaches have been used to modify the composition of microcapsules, by gradually incorporating extracellular matrix molecules (collagen IV, RGD), necrostatin-1, specific amino acids (alanine, glutamine, glycine). Additionally, pectin, a complex immunomodulating carbohydrate and supporter of mitochondrial health, can serve as an immune-attenuating biomaterial on capsule surfaces. Furthermore, pancreatic stellate cells were studied as a novel accessory cell to support the survival and function of β-cells.

The goal of Tian Qin's research is to maximize the longevity of transplanted islets post-transplantation. This is achieved by simulating a favorable microenvironment and reducing immune attacks. This dissertation presents new insights into creating novel composite microencapsulation and stromal cell support strategies to improve β-cell longevity, providing valuable data for the ultimate treatment of Type 1 diabetes with immuno-isolated islets.