Clinical pancreatic islet transplantation

Key Points

  • Pancreatic islet transplantation is an effective β-cell replacement therapy that has the capacity to normalize glycaemic control in patients with type 1 diabetes mellitus

  • To date, over 1,500 patients have undergone islet transplantation in approximately 40 international centres

  • The long-term clinical outcomes of islet transplantation alone in selected centres are now similar to the results of whole-pancreas transplantation alone, with 50–70% of patients achieving insulin independence at 5 years

  • An NIH funded phase III multicentre trial in North America has confirmed that islet transplantation is a safe and effective method for treatment of patients with type 1 diabetes mellitus complicated by hypoglycaemia unawareness and serve hypoglycaemic events

Abstract

Clinical pancreatic islet transplantation can be considered one of the safest and least invasive transplant procedures. Remarkable progress has occurred in both the technical aspects of islet cell processing and the outcomes of clinical islet transplantation. With >1,500 patients treated since 2000, this therapeutic strategy has moved from a curiosity to a realistic treatment option for selected patients with type 1 diabetes mellitus (that is, those with hypoglycaemia unawareness, severe hypoglycaemic episodes and glycaemic lability). This Review outlines the techniques required for human islet isolation, in vitro culture before the transplant and clinical islet transplantation, and discusses indications, optimization of recipient immunosuppression and management of adjunctive immunomodulatory and anti-inflammatory strategies. The potential risks, long-term outcomes and advances in treatment after the transplant are also discussed to further move this treatment towards becoming a more widely available option for patients with type 1 diabetes mellitus and eventually a potential cure.

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Figure 1: Timeline of pancreatic islet transplantation.
Figure 2: Schematic to illustrate entire process from islet isolation to intraportal transplantation.

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Acknowledgements

A.M.J.S. and C.R. are both supported through the NIH Clinical Islet Transplant (CIT) Consortium jointly funded through the National Institutes of Allergy, Immunology and Infectious Disease (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). A.M.J.S. holds a Canada Research Chair in Regenerative Medicine and Transplantation Surgery from the Canada Research Council, and is a Senior Clinical Scholar through Alberta Innovates Healthcare Solutions (AIHS). C.R. holds the Stacy Joy Goodman Chair in Diabetes Research and is supported in part by the Diabetes Research Institute Foundation (DRIF). Both A.M.J.S. and C.R. receive grant support through the Juvenile Diabetes Research Foundation (JDRF). The clinical islet transplant program at the University of Alberta receives support from Alberta Health Services, the Government of Alberta and through the Diabetes Research Institute Foundation of Canada (DRIFCan). The Diabetes Research Institute (DRI) at the University of Miami receives support from the DRIF, the JDRF and the Leona M. and Harry B. Helmsley Charitable Trust. Both centres in Edmonton and Miami are part of the Diabetes Research Institute Federation. A.M.J.S., M.P. and C.R. are members of The Cure Alliance. M.P. is supported through the National Science Center, Poland, National Center of Science and Development, Poland, and Minister of Science and High Education, Poland.

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Correspondence to A. M. James Shapiro or Camillo Ricordi.

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C.R. is co-inventor on patents related to pancreatic islet processing that are in part used for current islet cell product manufacturing. However, he is not receiving any royalty or financial benefit from these patents, or from islet cell processing activities. The other authors declare no competing interests.

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Shapiro, A., Pokrywczynska, M. & Ricordi, C. Clinical pancreatic islet transplantation. Nat Rev Endocrinol 13, 268–277 (2017). https://doi.org/10.1038/nrendo.2016.178

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