Co-transplantation of Human Pancreatic Islets With Post-migratory Neural Crest Stem Cells Increases beta-Cell Proliferation and Vascular And Neural Regrowth
2015 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 100, no 4, E583-E590 p.Article in journal (Refereed) Published
Context: Neural crest stem cells (NCSCs) are capable of substantially improving murine islet function by promoting beta-cell proliferation. Objective: The present study aimed to investigate the potential of NCSCs to stimulate human beta-cell proliferation, and improve neural and vascular engraftment of human islets. Design, Setting, and Subjects: Human pancreatic islets from 18 brain-dead cadaveric donors (age range, 19-78 y) were obtained through the Nordic Network for Clinical Islet Transplantation. beta-cell proliferation and graft function was investigated at our experimental laboratory. Intervention and Main Outcome Measures: Human islets were transplanted, either alone or together with spheres of NCSCs. beta-cell proliferation, as well as islet neuralandvascular densities, were assessed by immunohistochemistry. Graft blood perfusion and oxygen tension were measured using laser-Doppler flowmetry and Clark microelectrodes, respectively. Results: Two days posttransplantation, the number of Ki67-positive beta-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. Conclusion: We conclude that exposure to NCSCs stimulates human beta-cell proliferation, andthat these cells improve both the neural and vascular engraftment of transplanted human islets. NCSCs are a promising cellular therapy for translation into clinical use.
Place, publisher, year, edition, pages
2015. Vol. 100, no 4, E583-E590 p.
Endocrinology and Diabetes
IdentifiersURN: urn:nbn:se:uu:diva-253267DOI: 10.1210/jc.2014-4070ISI: 000353361500009PubMedID: 25668197OAI: oai:DiVA.org:uu-253267DiVA: diva2:813912