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Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells

During aging, senescent cells accumulate in various tissues accompanied by decreased regenerative capacities of quiescent stem cells, resulting in deteriorated organ function and overall degeneration. In this regard, the adult human heart with a generally low regenerative potential is of extreme int...

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Autores principales: Höving, Anna L., Schmidt, Kazuko E., Merten, Madlen, Hamidi, Jassin, Rott, Ann-Katrin, Faust, Isabel, Greiner, Johannes F. W., Gummert, Jan, Kaltschmidt, Barbara, Kaltschmidt, Christian, Knabbe, Cornelius
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349155/
https://www.ncbi.nlm.nih.gov/pubmed/32560212
http://dx.doi.org/10.3390/cells9061472
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author Höving, Anna L.
Schmidt, Kazuko E.
Merten, Madlen
Hamidi, Jassin
Rott, Ann-Katrin
Faust, Isabel
Greiner, Johannes F. W.
Gummert, Jan
Kaltschmidt, Barbara
Kaltschmidt, Christian
Knabbe, Cornelius
author_facet Höving, Anna L.
Schmidt, Kazuko E.
Merten, Madlen
Hamidi, Jassin
Rott, Ann-Katrin
Faust, Isabel
Greiner, Johannes F. W.
Gummert, Jan
Kaltschmidt, Barbara
Kaltschmidt, Christian
Knabbe, Cornelius
author_sort Höving, Anna L.
collection PubMed
description During aging, senescent cells accumulate in various tissues accompanied by decreased regenerative capacities of quiescent stem cells, resulting in deteriorated organ function and overall degeneration. In this regard, the adult human heart with a generally low regenerative potential is of extreme interest as a target for rejuvenating strategies with blood borne factors that might be able to activate endogenous stem cell populations. Here, we investigated for the first time the effects of human blood plasma and serum on adult human cardiac stem cells (hCSCs) and showed significantly increased proliferation capacities and metabolism accompanied by a significant decrease of senescent cells, demonstrating a beneficial serum-mediated effect that seemed to be independent of age and sex. However, RNA-seq analysis of serum-treated hCSCs revealed profound effects on gene expression depending on the age and sex of the plasma donor. We further successfully identified key pathways that are affected by serum treatment with p38-MAPK playing a regulatory role in protection from senescence and in the promotion of proliferation in a serum-dependent manner. Inhibition of p38-MAPK resulted in a decline of these serum-mediated beneficial effects on hCSCs in terms of decreased proliferation and accelerated senescence. In summary, we provide new insights in the regulatory networks behind serum-mediated protective effects on adult human cardiac stem cells.
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spelling pubmed-73491552020-07-22 Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells Höving, Anna L. Schmidt, Kazuko E. Merten, Madlen Hamidi, Jassin Rott, Ann-Katrin Faust, Isabel Greiner, Johannes F. W. Gummert, Jan Kaltschmidt, Barbara Kaltschmidt, Christian Knabbe, Cornelius Cells Article During aging, senescent cells accumulate in various tissues accompanied by decreased regenerative capacities of quiescent stem cells, resulting in deteriorated organ function and overall degeneration. In this regard, the adult human heart with a generally low regenerative potential is of extreme interest as a target for rejuvenating strategies with blood borne factors that might be able to activate endogenous stem cell populations. Here, we investigated for the first time the effects of human blood plasma and serum on adult human cardiac stem cells (hCSCs) and showed significantly increased proliferation capacities and metabolism accompanied by a significant decrease of senescent cells, demonstrating a beneficial serum-mediated effect that seemed to be independent of age and sex. However, RNA-seq analysis of serum-treated hCSCs revealed profound effects on gene expression depending on the age and sex of the plasma donor. We further successfully identified key pathways that are affected by serum treatment with p38-MAPK playing a regulatory role in protection from senescence and in the promotion of proliferation in a serum-dependent manner. Inhibition of p38-MAPK resulted in a decline of these serum-mediated beneficial effects on hCSCs in terms of decreased proliferation and accelerated senescence. In summary, we provide new insights in the regulatory networks behind serum-mediated protective effects on adult human cardiac stem cells. MDPI 2020-06-16 /pmc/articles/PMC7349155/ /pubmed/32560212 http://dx.doi.org/10.3390/cells9061472 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Höving, Anna L.
Schmidt, Kazuko E.
Merten, Madlen
Hamidi, Jassin
Rott, Ann-Katrin
Faust, Isabel
Greiner, Johannes F. W.
Gummert, Jan
Kaltschmidt, Barbara
Kaltschmidt, Christian
Knabbe, Cornelius
Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells
title Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells
title_full Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells
title_fullStr Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells
title_full_unstemmed Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells
title_short Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells
title_sort blood serum stimulates p38-mediated proliferation and changes in global gene expression of adult human cardiac stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349155/
https://www.ncbi.nlm.nih.gov/pubmed/32560212
http://dx.doi.org/10.3390/cells9061472
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