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

  1. Yizhe Tang
  2. Juan Pablo Zuniga-Hertz
  3. Cheng Han
  4. Bin Yu
  5. Dongsheng Cai  Is a corresponding author
  1. 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

  1. Yizhe Tang

    Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Juan Pablo Zuniga-Hertz

    Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Cheng Han

    Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Bin Yu

    Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Dongsheng Cai

    Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, United States
    For correspondence
    dongsheng.cai@einstein.yu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4187-1019

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)

Reviewing Editor

  1. Martin Pera, The Jackson Laboratory, United States

Version history

  1. Received: October 9, 2019
  2. Accepted: February 20, 2020
  3. Accepted Manuscript published: February 21, 2020 (version 1)
  4. Version of Record published: March 9, 2020 (version 2)
  5. Version of Record updated: April 16, 2020 (version 3)

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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  1. Yizhe Tang
  2. Juan Pablo Zuniga-Hertz
  3. Cheng Han
  4. Bin Yu
  5. Dongsheng Cai
(2020)
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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https://doi.org/10.7554/eLife.52580

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