Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/52580 |
| _version_ | 1828195492858691584 |
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| author | Yizhe Tang Juan Pablo Zuniga-Hertz Cheng Han Bin Yu Dongsheng Cai |
| author_facet | Yizhe Tang Juan Pablo Zuniga-Hertz Cheng Han Bin Yu Dongsheng Cai |
| author_sort | Yizhe Tang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:44:36Z |
| format | Article |
| id | doaj.art-b32c5788c3fe43969c2f98a9c0627225 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:44:36Z |
| publishDate | 2020-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b32c5788c3fe43969c2f98a9c06272252022-12-22T03:37:59ZengeLife Sciences Publications LtdeLife2050-084X2020-02-01910.7554/eLife.52580Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in miceYizhe Tang0Juan Pablo Zuniga-Hertz1Cheng Han2Bin Yu3Dongsheng Cai4https://orcid.org/0000-0002-4187-1019Department of Molecular Pharmacology, Diabetes Research Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Molecular Pharmacology, Diabetes Research Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Molecular Pharmacology, Diabetes Research Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Molecular Pharmacology, Diabetes Research Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Molecular Pharmacology, Diabetes Research Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, United StatesWe 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.https://elifesciences.org/articles/52580hypothalamusneural stem cellimplantationexosomeinsulindiabetes |
| spellingShingle | Yizhe Tang Juan Pablo Zuniga-Hertz Cheng Han Bin Yu Dongsheng Cai Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice eLife hypothalamus neural stem cell implantation exosome insulin diabetes |
| title | Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice |
| title_full | Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice |
| title_fullStr | Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice |
| title_full_unstemmed | Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice |
| title_short | Multifaceted secretion of htNSC-derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice |
| title_sort | multifaceted secretion of htnsc derived hypothalamic islets induces survival and antidiabetic effect via peripheral implantation in mice |
| topic | hypothalamus neural stem cell implantation exosome insulin diabetes |
| url | https://elifesciences.org/articles/52580 |
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