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Author Spotlight: Techniques and Challenges in Islet Purification for Xenotransplantation
Published on: June 7, 2024
Construction of EMSC-islet co-localizing composites for xenogeneic porcine islet transplantation
Jung-Sik Kim1, Hyunwoo Chung2, Nari Byun2
1Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul 110-799, South Korea; Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 110-799, South Korea; Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 110-799, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, South Korea.
Abstract:
Pancreatic islet transplantation is an ultimate solution for treating patients with type 1 diabetes (T1D). The pig is an ideal donor of islets for replacing scarce human islets. Besides immunological hurdles, non-immunological hurdles including fragmentation and delayed engraftment of porcine islets need solutions to succeed in porcine islet xenotransplantation. In this study, we suggest a simple but effective modality, a cell/islet co-localizing composite, to overcome these challenges. Endothelial-like mesenchymal stem cells (EMSCs), differentiated from bone-marrow derived mouse mesenchymal stem cells (MSCs), and MSCs evenly coated the surface of porcine islets (>85%) through optimized culture conditions. Both MSCs and EMSCs significantly reduced the fragmentation of porcine islets and increased the islet masses, designated as islet equivalents (IEQs). In fibrin in vitro and in vivo angiogenesis analysis, constructed EMSC-islet composites showed higher angiogenic potentials than naked islets, MSC-islet composites, or human endothelial cell-islet composites. This novel delivery method of porcine islets may have beneficial effects on the engraftment of transplanted islets by prevention of fragmentation and enhancement of revascularization.
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