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Increasing cytosolic Ca(2+) levels restore cell proliferation and stem cell potency in aged MSCs
Aging is an inescapable complex physiological but extendable process, and all cells, including stem cells, are altered over time. Diverse mechanism(s) could modulate stem cell number, their proliferation rate, and promote tissue repair during aging that leads to longevity. However, the factors that...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596392/ https://www.ncbi.nlm.nih.gov/pubmed/34624617 http://dx.doi.org/10.1016/j.scr.2021.102560 |
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author | Ahamad, Naseem Sun, Yuyang Singh, Brij B. |
author_facet | Ahamad, Naseem Sun, Yuyang Singh, Brij B. |
author_sort | Ahamad, Naseem |
collection | PubMed |
description | Aging is an inescapable complex physiological but extendable process, and all cells, including stem cells, are altered over time. Diverse mechanism(s) could modulate stem cell number, their proliferation rate, and promote tissue repair during aging that leads to longevity. However, the factors that could restore aging stem cell potency and would lead to healthy aging are not fully identified. Here we show that maintaining cytosolic Ca(2+) levels was essential for modulating stem cells function in aged mesenchymal stem cells (MSCs). Increasing external Ca(2+) induced spindle shape stem cell morphology and maintained stem cell surface marker expression in aged bone marrow-derived MSCs. Similarly, stem cell survival and proliferation of aged MSCs was dependent on cytosolic Ca(2+) levels. Importantly, Ca(2+) entry potentiated cell cycle progression, and stem cell potential was increased in cells incubated with higher external Ca(2+). Moreover, blocking Ca(2+) entry using SKF 96365, decreased stem cell survival and its proliferation but, treatment with 2-APB did not significantly affected cell proliferation, rather only modulated cell viability. Evaluation of Ca(2+) entry channels, showed that TRPC1/Orai1/Orai3 and their regulator STIM1 was essential for MSCs proliferation/viability as gene silencing of Orai1/Orai3/TRPC1/STIM1 significantly inhibited stem cell viability. Finally, MSCs isolated from aged mice that were subjected to higher Ca(2+) levels, were able to rescue age-induced loss of MSCs function. Together these results suggest that Ca(2+) entry is essential for preventing the loss of aged stem cell function and supplementing Ca(2+) not only restored their proliferative potential but, allowed them to develop into younger stem cell lineages that could be critical for regenerative medicine. |
format | Online Article Text |
id | pubmed-8596392 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-85963922021-11-17 Increasing cytosolic Ca(2+) levels restore cell proliferation and stem cell potency in aged MSCs Ahamad, Naseem Sun, Yuyang Singh, Brij B. Stem Cell Res Article Aging is an inescapable complex physiological but extendable process, and all cells, including stem cells, are altered over time. Diverse mechanism(s) could modulate stem cell number, their proliferation rate, and promote tissue repair during aging that leads to longevity. However, the factors that could restore aging stem cell potency and would lead to healthy aging are not fully identified. Here we show that maintaining cytosolic Ca(2+) levels was essential for modulating stem cells function in aged mesenchymal stem cells (MSCs). Increasing external Ca(2+) induced spindle shape stem cell morphology and maintained stem cell surface marker expression in aged bone marrow-derived MSCs. Similarly, stem cell survival and proliferation of aged MSCs was dependent on cytosolic Ca(2+) levels. Importantly, Ca(2+) entry potentiated cell cycle progression, and stem cell potential was increased in cells incubated with higher external Ca(2+). Moreover, blocking Ca(2+) entry using SKF 96365, decreased stem cell survival and its proliferation but, treatment with 2-APB did not significantly affected cell proliferation, rather only modulated cell viability. Evaluation of Ca(2+) entry channels, showed that TRPC1/Orai1/Orai3 and their regulator STIM1 was essential for MSCs proliferation/viability as gene silencing of Orai1/Orai3/TRPC1/STIM1 significantly inhibited stem cell viability. Finally, MSCs isolated from aged mice that were subjected to higher Ca(2+) levels, were able to rescue age-induced loss of MSCs function. Together these results suggest that Ca(2+) entry is essential for preventing the loss of aged stem cell function and supplementing Ca(2+) not only restored their proliferative potential but, allowed them to develop into younger stem cell lineages that could be critical for regenerative medicine. 2021-10-03 2021-10 /pmc/articles/PMC8596392/ /pubmed/34624617 http://dx.doi.org/10.1016/j.scr.2021.102560 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Ahamad, Naseem Sun, Yuyang Singh, Brij B. Increasing cytosolic Ca(2+) levels restore cell proliferation and stem cell potency in aged MSCs |
title | Increasing cytosolic Ca(2+) levels restore cell proliferation and stem cell potency in aged MSCs |
title_full | Increasing cytosolic Ca(2+) levels restore cell proliferation and stem cell potency in aged MSCs |
title_fullStr | Increasing cytosolic Ca(2+) levels restore cell proliferation and stem cell potency in aged MSCs |
title_full_unstemmed | Increasing cytosolic Ca(2+) levels restore cell proliferation and stem cell potency in aged MSCs |
title_short | Increasing cytosolic Ca(2+) levels restore cell proliferation and stem cell potency in aged MSCs |
title_sort | increasing cytosolic ca(2+) levels restore cell proliferation and stem cell potency in aged mscs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596392/ https://www.ncbi.nlm.nih.gov/pubmed/34624617 http://dx.doi.org/10.1016/j.scr.2021.102560 |
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