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Article

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

1
Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea
2
King Abdullah University of Science and Technology, Thuwal 47000, Makkah Province, Saudi Arabia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2021, 10(1), 63; https://doi.org/10.3390/cells10010063
Received: 19 November 2020 / Revised: 28 December 2020 / Accepted: 29 December 2020 / Published: 3 January 2021
(This article belongs to the Special Issue Chronic Inflammation, Oxidative Stress and Adult Stem Cells)
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. View Full-Text
Keywords: small cell; mesenchymal stem cell senescence; senescence-associated secretory phenotype; growth-regulated oncogene-alpha; interukin-8; C-X-C motif chemokine receptor 2; toll-like receptor 2; toll-like receptor 5; cell-based therapy small cell; mesenchymal stem cell senescence; senescence-associated secretory phenotype; growth-regulated oncogene-alpha; interukin-8; C-X-C motif chemokine receptor 2; toll-like receptor 2; toll-like receptor 5; cell-based therapy
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MDPI and ACS Style

Kwon, J.H.; Kim, M.; Um, S.; Lee, H.J.; Bae, Y.K.; Choi, S.J.; Hwang, H.H.; Oh, W.; Jin, H.J. Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling. Cells 2021, 10, 63. https://doi.org/10.3390/cells10010063

AMA Style

Kwon JH, Kim M, Um S, Lee HJ, Bae YK, Choi SJ, Hwang HH, Oh W, Jin HJ. Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling. Cells. 2021; 10(1):63. https://doi.org/10.3390/cells10010063

Chicago/Turabian Style

Kwon, Ji H., Miyeon Kim, Soyoun Um, Hyang J. Lee, Yun K. Bae, Soo J. Choi, Hyun H. Hwang, Wonil Oh, and Hye J. Jin 2021. "Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling" Cells 10, no. 1: 63. https://doi.org/10.3390/cells10010063

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