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

Yizhe Tang, Juan Pablo Hertz Zuniga, Cheng Han, Bin Yu, Dongsheng Cai

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere52580
JournaleLife
Volume9
DOIs
StatePublished - Feb 2020

Keywords

  • Diabetes
  • Exosome
  • Hypothalamus
  • Implantation
  • Insulin
  • Neural stem cell

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice'. Together they form a unique fingerprint.

  • Cite this