Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice

eLife

Cheng Han¹  Juan Pablo Zuniga-Hertz¹  Yizhe Tang¹  Dongsheng Cai¹  Bin Yu¹ 

[1] Department of Molecular Pharmacology, Diabetes Research Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, United States;

关键词: hypothalamus;    neural stem cell;    implantation;    exosome;    insulin;    diabetes;   

DOI  :  10.7554/eLife.52580

来源: DOAJ

【 摘 要 】

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(s) 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 their derived hypothalamic islets can be implanted peripherally to enhance general health and survival together with an antidiabetic benefit.

【 授权许可】

Unknown