Intracutaneous Transplantation of Islets Within a Biodegradable Temporizing Matrix as an Alternative Site for Islet Transplantation.

Autor:	Rojas-Canales D; Department of Medicine, University of Adelaide, Royal Adelaide Hospital Campus, Adelaide, South Australia, Australia.; Central Northern Adelaide Renal and Transplantation Services, Royal Adelaide Hospital, Adelaide, South Australia, Australia., Walters SN; Transplantation Immunology Laboratory, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia., Penko D; Department of Medicine, University of Adelaide, Royal Adelaide Hospital Campus, Adelaide, South Australia, Australia.; Central Northern Adelaide Renal and Transplantation Services, Royal Adelaide Hospital, Adelaide, South Australia, Australia., Cultrone D; Transplantation Immunology Laboratory, Garvan Institute of Medical Research, Sydney, New South Wales, Australia., Bailey J; Transplantation Immunology Laboratory, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia., Chtanova T; Transplantation Immunology Laboratory, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia., Nitschke J; Department of Medicine, University of Adelaide, Royal Adelaide Hospital Campus, Adelaide, South Australia, Australia.; Central Northern Adelaide Renal and Transplantation Services, Royal Adelaide Hospital, Adelaide, South Australia, Australia., Johnston J; Department of Medicine, University of Adelaide, Royal Adelaide Hospital Campus, Adelaide, South Australia, Australia.; Central Northern Adelaide Renal and Transplantation Services, Royal Adelaide Hospital, Adelaide, South Australia, Australia., Kireta S; Department of Medicine, University of Adelaide, Royal Adelaide Hospital Campus, Adelaide, South Australia, Australia.; Central Northern Adelaide Renal and Transplantation Services, Royal Adelaide Hospital, Adelaide, South Australia, Australia., Loudovaris T; St. Vincent's Institute, Melbourne, Victoria, Australia., Kay TW; St. Vincent's Institute, Melbourne, Victoria, Australia., Kuchel TR; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia., Hawthorne W; Westmead Hospital Sydney, Sydney, New South Wales, Australia., O'Connell PJ; Westmead Hospital Sydney, Sydney, New South Wales, Australia., Korbutt G; University of Alberta, Edmonton, Alberta, Canada., Greenwood JE; Burns Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia., Grey ST; Transplantation Immunology Laboratory, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia., Drogemuller CJ; Department of Medicine, University of Adelaide, Royal Adelaide Hospital Campus, Adelaide, South Australia, Australia.; Central Northern Adelaide Renal and Transplantation Services, Royal Adelaide Hospital, Adelaide, South Australia, Australia., Coates PT; Department of Medicine, University of Adelaide, Royal Adelaide Hospital Campus, Adelaide, South Australia, Australia.; Central Northern Adelaide Renal and Transplantation Services, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2023 Jun 01; Vol. 72 (6), pp. 758-768.
DOI:	10.2337/db21-0841
Abstrakt:	Intrahepatic islet transplantation for type 1 diabetes is limited by the need for multiple infusions and poor islet viability posttransplantation. The development of alternative transplantation sites is necessary to improve islet survival and facilitate monitoring and retrieval. We tested a clinically proven biodegradable temporizing matrix (BTM), a polyurethane-based scaffold, to generate a well-vascularized intracutaneous "neodermis" within the skin for islet transplantation. In murine models, BTM did not impair syngeneic islet renal-subcapsular transplant viability or function, and it facilitated diabetes cure for over 150 days. Furthermore, BTM supported functional neonatal porcine islet transplants into RAG-1-/- mice for 400 days. Hence, BTM is nontoxic for islets. Two-photon intravital imaging used to map vessel growth through time identified dense vascular networks, with significant collagen deposition and increases in vessel mass up to 30 days after BTM implantation. In a preclinical porcine skin model, BTM implants created a highly vascularized intracutaneous site by day 7 postimplantation. When syngeneic neonatal porcine islets were transplanted intracutaneously, the islets remained differentiated as insulin-producing cells, maintained normal islet architecture, secreted c-peptide, and survived for over 100 days. Here, we show that BTM facilitates formation of an islet-supportive intracutaneous neodermis in a porcine preclinical model, as an alternative islet-transplant site. Article Highlights: Human and porcine pancreatic islets were transplanted into a fully vascularized biodegradable temporizing matrix (Novosorb) that creates a unique intracutaneous site outside of the liver in a large-animal preclinical model. The intracutaneous prevascularized site supported pancreatic islet survival for 3 months in a syngeneic porcine-transplant model. Pancreatic (human and porcine) islet survival and function were demonstrated in an intracutaneous site outside of the liver for the first time in a large-animal preclinical model. (© 2023 by the American Diabetes Association.)
Databáze:	MEDLINE
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