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Ludwig, B. ; Heller, C. ; Sarangova, V.* ; Welzel, P.B.*

Islet macroencapsulation: Strategies to boost islet graft oxygenation.

In: Pluripotent Stem Cell Therapy for Diabetes. 2024. 251-280 (Pluripotent Stem Cell Therapy for Diabetes, First Edition)

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Islet transplantation is a valid therapy for patients with type 1 diabetes. However, a widespread application is hampered by mandatory requirement of life-long immunosuppression, the shortage of cadaveric donor organs, and the limited long-term efficacy. Therefore, safe utilization of alternative cell sources, eliminating immunosuppression, and promoting long-term islet survival are key features for moving this therapy to larger scale application. Macroencapsulation devices as delivery vehicles could potentially target these challenges. Numerous encapsulation devices have been designed that combine immunoprotective properties and allow for exchange of effector molecules. Major advances have been achieved in encapsulation technology, and some strategies are in translation to clinical application. However, these still face issues that need to be resolved associated with biocompatibility, graft oxygenation, immunoprotection, inflammatory response, and the applicable islet mass. Here, we elucidate key aspects that need to be considered for the development of a successful macroencapsulation device. Overarching determinants are the diffusion characteristics of the device components and the oxygenation of the cell implant. All device design aspects from macro- and microarchitecture to material selection and transplantation site affect these features and thereby determine engraftment, functional potency and long-term efficiency.

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