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Liza Grapensparr, Svitlana Vasylovska, Zhanchun Li, Johan Olerud, Leif Jansson, Elena Kozlova, Per-Ola Carlsson, Co-transplantation of Human Pancreatic Islets With Post-migratory Neural Crest Stem Cells Increases β-Cell Proliferation and Vascular And Neural Regrowth, The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 4, April 2015, Pages E583–E590, https://doi.org/10.1210/jc.2014-4070
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Neural crest stem cells (NCSCs) are capable of substantially improving murine islet function by promoting β-cell proliferation.
The present study aimed to investigate the potential of NCSCs to stimulate human β-cell proliferation, and improve neural and vascular engraftment of human islets.
Human pancreatic islets from 18 brain-dead cadaveric donors (age range, 19–78 y) were obtained through the Nordic Network for Clinical Islet Transplantation. β-cell proliferation and graft function was investigated at our experimental laboratory.
Human islets were transplanted, either alone or together with spheres of NCSCs. β-cell proliferation, as well as islet neural and vascular densities, were assessed by immunohistochemistry. Graft blood perfusion and oxygen tension were measured using laser-Doppler flowmetry and Clark microelectrodes, respectively.
Two days posttransplantation, the number of Ki67-positive β-cells was doubled in human islets that had been exposed to NCSCs. Similar findings were obtained in vitro, as well as with EdU as proliferation marker. Four weeks posttransplantation, NCSC-exposed human islet grafts had much higher neural and vascular densities. The newly formed blood vessels were also functional, given that these human islets had a substantially higher blood perfusion and oxygen tension when compared with control transplants.
We conclude that exposure to NCSCs stimulates human β-cell proliferation, and that these cells improve both the neural and vascular engraftment of transplanted human islets. NCSCs are a promising cellular therapy for translation into clinical use.
