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Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling

In order to provide a sufficient number of cells for clinical use, mesenchymal stem cells (MSCs) must be cultured for long-term expansion, which inevitably triggers cellular senescence. Although the small size of MSCs is known as a critical determinant of their fate, the main regulators of stem cell...

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Autores principales: Kwon, Ji Hye, Kim, Miyeon, Um, Soyoun, Lee, Hyang Ju, Bae, Yun Kyung, Choi, Soo Jin, Hwang, Hyun Ho, Oh, Wonil, Jin, Hye Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824096/
https://www.ncbi.nlm.nih.gov/pubmed/33401590
http://dx.doi.org/10.3390/cells10010063
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author Kwon, Ji Hye
Kim, Miyeon
Um, Soyoun
Lee, Hyang Ju
Bae, Yun Kyung
Choi, Soo Jin
Hwang, Hyun Ho
Oh, Wonil
Jin, Hye Jin
author_facet Kwon, Ji Hye
Kim, Miyeon
Um, Soyoun
Lee, Hyang Ju
Bae, Yun Kyung
Choi, Soo Jin
Hwang, Hyun Ho
Oh, Wonil
Jin, Hye Jin
author_sort Kwon, Ji Hye
collection PubMed
description In order to provide a sufficient number of cells for clinical use, mesenchymal stem cells (MSCs) must be cultured for long-term expansion, which inevitably triggers cellular senescence. Although the small size of MSCs is known as a critical determinant of their fate, the main regulators of stem cell senescence and the underlying signaling have not been addressed. Umbilical cord blood-derived MSCs (UCB-MSCs) were obtained using size-isolation methods and then cultured with control or small cells to investigate the major factors that modulate MSC senescence. Cytokine array data suggested that the secretion of interukin-8 (IL-8) or growth-regulated oncogene-alpha (GROa) by senescent cells was markedly inhibited during incubation of small cells along with suppression of cognate receptor (C-X-C motif chemokine receptor2, CXCR2) via blockade of the autocrine/paracrine positive loop. Moreover, signaling via toll-like receptor 2 (TLR2) and TLR5, both pattern recognition receptors, drove cellular senescence of MSCs, but was inhibited in small cells. The activation of TLRs (2 and 5) through ligand treatment induced a senescent phenotype in small cells. Collectively, our data suggest that small cell from UCB-MSCs exhibit delayed cellular senescence by inhibiting the process of TLR signaling-mediated senescence-associated secretory phenotype (SASP) activation.
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spelling pubmed-78240962021-01-24 Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling Kwon, Ji Hye Kim, Miyeon Um, Soyoun Lee, Hyang Ju Bae, Yun Kyung Choi, Soo Jin Hwang, Hyun Ho Oh, Wonil Jin, Hye Jin Cells Article In order to provide a sufficient number of cells for clinical use, mesenchymal stem cells (MSCs) must be cultured for long-term expansion, which inevitably triggers cellular senescence. Although the small size of MSCs is known as a critical determinant of their fate, the main regulators of stem cell senescence and the underlying signaling have not been addressed. Umbilical cord blood-derived MSCs (UCB-MSCs) were obtained using size-isolation methods and then cultured with control or small cells to investigate the major factors that modulate MSC senescence. Cytokine array data suggested that the secretion of interukin-8 (IL-8) or growth-regulated oncogene-alpha (GROa) by senescent cells was markedly inhibited during incubation of small cells along with suppression of cognate receptor (C-X-C motif chemokine receptor2, CXCR2) via blockade of the autocrine/paracrine positive loop. Moreover, signaling via toll-like receptor 2 (TLR2) and TLR5, both pattern recognition receptors, drove cellular senescence of MSCs, but was inhibited in small cells. The activation of TLRs (2 and 5) through ligand treatment induced a senescent phenotype in small cells. Collectively, our data suggest that small cell from UCB-MSCs exhibit delayed cellular senescence by inhibiting the process of TLR signaling-mediated senescence-associated secretory phenotype (SASP) activation. MDPI 2021-01-03 /pmc/articles/PMC7824096/ /pubmed/33401590 http://dx.doi.org/10.3390/cells10010063 Text en © 2021 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
Kwon, Ji Hye
Kim, Miyeon
Um, Soyoun
Lee, Hyang Ju
Bae, Yun Kyung
Choi, Soo Jin
Hwang, Hyun Ho
Oh, Wonil
Jin, Hye Jin
Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling
title Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling
title_full Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling
title_fullStr Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling
title_full_unstemmed Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling
title_short Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling
title_sort senescence-associated secretory phenotype suppression mediated by small-sized mesenchymal stem cells delays cellular senescence through tlr2 and tlr5 signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824096/
https://www.ncbi.nlm.nih.gov/pubmed/33401590
http://dx.doi.org/10.3390/cells10010063
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