TY - JOUR TI - Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice AU - Tang, Yizhe AU - Zuniga-Hertz, Juan Pablo AU - Han, Cheng AU - Yu, Bin AU - Cai, Dongsheng A2 - Pera, Martin A2 - Bronner, Marianne E A2 - Tong, Qingchun VL - 9 PY - 2020 DA - 2020/02/21 SP - e52580 C1 - eLife 2020;9:e52580 DO - 10.7554/eLife.52580 UR - https://doi.org/10.7554/eLife.52580 AB - 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. KW - hypothalamus KW - neural stem cell KW - implantation KW - exosome KW - insulin KW - diabetes JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -