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

Cells

Miyeon Kim¹  SooJin Choi¹  Wonil Oh¹  YunKyung Bae¹  HyeJin Jin¹  HyangJu Lee¹  Soyoun Um¹  JiHye Kwon¹  HyunHo Hwang² 

[1] Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea;King Abdullah University of Science and Technology, Thuwal 47000, Makkah Province, Saudi Arabia;

关键词: small cell;    mesenchymal stem cell senescence;    senescence-associated secretory phenotype;    growth-regulated oncogene-alpha;    interukin-8;    C-X-C motif chemokine receptor 2;   

DOI  :  10.3390/cells10010063

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown