期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 100, 期 4, 页码 E583-E590出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2014-4070
关键词
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资金
- Nordic Network for Clinical Islet Transplantation
- Swedish Research Council [521-2011-377, 20716, 55X-15043]
- Excellence of Diabetes Research in Sweden (EXODIAB)
- European Foundation for the Study of Diabetes/JDRF/Novo Nordisk Programme
- Swedish Diabetes Association
- Diabetes Wellness Sverige
- Swedish Institute Visby Programme
- Novo Nordisk Foundation
- Olle Engqvist Byggmastare Fund
- AFA Insurances
- Family Ernfors Fund
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.
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