Beta cell replacement has the potential to restore euglycemia in patients with insulin-dependent diabetes. Although great progress has been made in establishing allogeneic islet transplantation from deceased donors as the standard of care for those with the most labile diabetes, it is also clear that the deceased donor organ supply cannot possibly treat all those who could benefit from restoration of a normal beta cell mass, especially if immunosuppression were not required. Against this background, the International Pancreas and Islet Transplant Association in collaboration with the Harvard Stem Cell Institute, the Juvenile Diabetes Research Foundation (JDRF), and the Helmsley Foundation held a 2-day Key Opinion Leaders Meeting in Boston in 2016 to bring together experts in generating and transplanting beta cells derived from stem cells. The following summary highlights current technology, recent significant breakthroughs, unmet needs and roadblocks to stem cell-derived beta cell therapies, with the aim of spurring future preclinical collaborative investigations and progress toward the clinical application of stem cell-derived beta cells.
Bibliographical noteFunding Information:
Jose Oberholzer9 is studying the functionality and heterogeneity of stem cell–derived beta cells using biochip-based microfluidic and nanofluidic, multiparametric perifusion assays designed to study beta cell physiology and to phenotype islet surrogates from various sources. The islet biochips integrate islet micro and nanoperifusion with multiparametric imaging technology and measure not only insulin secretion kinetics but also insulin secretion coupling which is determined by measuring calcium influx and mitochondrial potentials. Integrated high throughput islet arrays and multiplexing have significantly increased the analytical power of these biochips, providing better understanding of the heterogeneity of stem cell–derived islet surrogates. Oberholzer's beta cell testing facility is funded by the Juvenile Diabetes Research Foundation (JDRF) and is available to test various beta cell or islet surrogate populations. However, the correlation of test results with in vivo function is still under study.
The authors would like to acknowledge the generous support for thisWorkshop provided by the International Pancreas and Islet Transplant Association, the Juvenile Diabetes Research Foundation/Helmsley Charitable Trust, Harvard Stem Cell Institute, Novo Nordisk, Sanofi, Massachusetts GeneralHospital Transplant Center, Evotec, Preclinical Medevice Innovations (PMI), BetaO2 Technologies, Novartis, and Merck.
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PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't