Jung-Sik Kim1,2,3,4, Youngmee Jung5, Su Hee Kim5, Jun-Seop Shin1,2,3, Soo Hyun Kim5, Chung-Gyu Park1,2,4,6,7. 1. Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, Korea. 2. Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea. 3. Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul, Korea. 4. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. 5. Biomaterials Research Center, Korea Institute of Science and Technology, Seoul, Korea. 6. Biomedical Research Institute, Seoul National University College of Medicine, Seoul, Korea. 7. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
Abstract
BACKGROUND: Subcutaneous tissue is an attractive extra-hepatic heterotopic site for islet transplantation; however, poor oxygen tension and blood supply during early engraftment of implanted islets have limited the use of this site in clinical applications. METHODS: This study investigated the vascularization potential of hypoxia-preconditioned mesenchymal stem cells (3% O2 ; hypo-MSCs) in PLGA-based bio-artificial beds for subsequent subcutaneous islet transplantation. Sheet-typed polymeric PLGA scaffolds coated with hypo-MSCs or normo-MSCs (MSCs cultured under normoxia conditions, 21% O2 ) were implanted subcutaneously in mice. RESULTS: Compared to normo-MSCs, hypo-MSCs significantly enhanced vasculogenesis, both on the interior and exterior surfaces of the implanted PLGA devices, which peaked 4 weeks after implantation. Further, infusion of porcine islets inside the prevascularized PLGA bed restored normal glycemic control in 6 of 6 STZ-induced diabetic mice. The mass of the marginal islet was approximately 2000 IEQs, which is comparable to that required for the renal subcapsular space, a highly vascularized site. CONCLUSIONS: Therefore, PLGA-based bio-artificial devices prevascularized with hypo-MSCs could be a useful modality for successful subcutaneous islet transplantation, which is of high clinical relevance.
BACKGROUND: Subcutaneous tissue is an attractive extra-hepatic heterotopic site for islet transplantation; however, poor oxygen tension and blood supply during early engraftment of implanted islets have limited the use of this site in clinical applications. METHODS: This study investigated the vascularization potential of hypoxia-preconditioned mesenchymal stem cells (3% O2 ; hypo-MSCs) in PLGA-based bio-artificial beds for subsequent subcutaneous islet transplantation. Sheet-typed polymeric PLGA scaffolds coated with hypo-MSCs or normo-MSCs (MSCs cultured under normoxia conditions, 21% O2 ) were implanted subcutaneously in mice. RESULTS: Compared to normo-MSCs, hypo-MSCs significantly enhanced vasculogenesis, both on the interior and exterior surfaces of the implanted PLGA devices, which peaked 4 weeks after implantation. Further, infusion of porcine islets inside the prevascularized PLGA bed restored normal glycemic control in 6 of 6 STZ-induced diabeticmice. The mass of the marginal islet was approximately 2000 IEQs, which is comparable to that required for the renal subcapsular space, a highly vascularized site. CONCLUSIONS: Therefore, PLGA-based bio-artificial devices prevascularized with hypo-MSCs could be a useful modality for successful subcutaneous islet transplantation, which is of high clinical relevance.
Authors: Jaekyung Koh; Donald R Griffin; Maani M Archang; An-Chieh Feng; Thomas Horn; Michael Margolis; David Zalazar; Tatiana Segura; Philip O Scumpia; Dino Di Carlo Journal: Small Date: 2019-08-13 Impact factor: 13.281