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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
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
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