Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice
- Albert Einstein College of Medicine, United States
Abstract
We report that mouse hypothalamic stem/progenitor cells produce multiple pancreatic, gastrointestinal and hypothalamic peptides in addition to exosomes. Through cell sorting and selection according to insulin promoter activity, we generated a subpopulation of these cells which formed 3D spherical structure with combined features of hypothalamic neurospheres and pancreatic islets. Through testing streptozotocin-induced pancreatic islet disruption and fatal diabetes, we found that peripheral implantation of these spheres in mice led to remarkable improvements in general health and survival in addition to a moderate antidiabetic effect, and notably these pro-survival versus metabolic effects were dissociable to a significant extent. Mechanistically, secretion of exosomes by these spheres was essential for enhancing survival while production of insulin was important for the antidiabetic effect. In summary, hypothalamic neural stem/progenitor cells comprise subpopulations with multifaceted secretion, and this subpopulation-derived hypothalamic islets can be implanted peripherally to enhance general health and survival together with an antidiabetic benefit.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
National Institute on Aging (AG031774)
- Dongsheng Cai
National Institute of Diabetes and Digestive and Kidney Diseases (DK099136)
- Dongsheng Cai
National Heart, Lung, and Blood Institute (HL147477)
- Dongsheng Cai
National Institute of Diabetes and Digestive and Kidney Diseases (DK121435)
- Dongsheng Cai
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal procedures in this study were approved by the IACUC of Albert Einstein College of Medicine. (protocol #20171210, #20170812, #20171209, #20171208, #00001111)
Copyright
© 2020, Tang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice
eLife 9:e52580.
https://doi.org/10.7554/eLife.52580
