Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling.
AuthorsKwon, Ji Hye
Lee, Hyang Ju
Bae, Yun Kyung
Choi, Soo Jin
Hwang, Hyun Ho
Jin, Hye Jin
KAUST DepartmentPublication Srvcs and Researcher Support
Permanent link to this recordhttp://hdl.handle.net/10754/666895
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AbstractIn 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.
CitationKwon, J. H., Kim, M., Um, S., Lee, H. J., Bae, Y. K., Choi, S. J., … Jin, H. J. (2021). Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling. Cells, 10(1), 63. doi:10.3390/cells10010063
SponsorsThis research was funded by the Science Research Program through the National Research Foundation of Korea (NRF), grant number NRF-2018R1CB6001767.
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