Transplant strategies for type 1 diabetes: whole pancreas, islet and porcine beta cell therapies
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REVIEW
Transplant strategies for type 1 diabetes: whole pancreas, islet and porcine beta cell therapies Melena D. Bellin 1,2
&
Ty B. Dunn 3
Received: 9 March 2020 / Accepted: 14 April 2020 / Published online: 31 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Whole-organ pancreas and islet transplantations are performed in a highly selected group of patients with diabetes mellitus, primarily those with type 1 diabetes mellitus, complicated by recurrent severe hypoglycaemia or renal failure requiring kidney transplantation. Clinical accessibility to pancreases or islets, and patient characteristics and therapeutic goals, may dictate choice of procedure. Pancreas transplantation is most often performed simultaneous with a kidney transplant, but patients with particularly labile type 1 diabetes may be considered for a pancreas transplant alone. While highly successful at restoring insulin independence, pancreas transplants carry the significant risks of major surgery and immunosuppression. Islet transplantation is a relatively minor procedure, usually performed for labile type 1 diabetes with severe hypoglycaemia. It is highly successful at resolving hypoglycaemia, but more than one pancreas donor may be required for insulin independence. Both pancreas and islet transplantation are limited in applicability by a paucity of deceased donors. Pigs provide one promising replenishable source of islets. Porcine islets can successfully reverse diabetes mellitus in non-human primates under the appropriate immunosuppressive conditions, with promise for eventually translating this success to a larger population of patients with diabetes mellitus in the future.
Keywords Diabetes . Hypoglycaemia . Immunosuppression . Islet . Kidney . Pancreas . Transplant . Type 1 diabetes Abbreviations CFRD Cystic fibrosis-related diabetes CIT Clinical Islet Transplant CNI Calcineurin inhibitor IBMIR Instant blood-mediated inflammatory response ITA Islet transplant alone PAK Pancreas-after-kidney PERV Porcine endogenous retrovirus Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-020-05184-7) contains a slide of the figure for download, which is available to authorised users. * Melena D. Bellin [email protected] 1
Medical School, University of Minnesota, Minneapolis, MN, USA
2
Department of Pediatrics, University of Minnesota Masonic Children’s Hospital, East Building Rm MB 671, 2450 Riverside Ave S, Minneapolis, MN 55454, USA
3
Department of Surgery, Division of Transplantation, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, USA
PTA SPK
Pancreas transplant alone Simultaneous pancreas–kidney
Introduction Despite advancements in insulin analogues, continuous glucose monitors and closed-loop insulin pump technology, treatment of type 1 diabetes mellitus with exogenous insulin remains complicated by hyperglycaemia and hypoglycaemia. For selected patients with diabetes mellitus who require kidney transplant or who experience rec
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