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

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 1; p. 63
• Main Authors: Kwon, Ji Hye, Kim, Miyeon, Um, Soyoun, Lee, Hyang Ju, Bae, Yun Kyung, Choi, Soo Jin, Hwang, Hyun Ho, Oh, Wonil, Jin, Hye Jin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.01.2021; MDPI
• Subjects: Antibodies; Ataxia; Autocrine signalling; C-X-C motif chemokine receptor 2; Cell activation; Cell culture; Chemokines; Cord blood; CXCR2 protein; Cytokines; Deoxyribonucleic acid; DNA; DNA methylation; Enzymes; growth-regulated oncogene-alpha; Interleukin 8; interukin-8; Kinases; mesenchymal stem cell senescence; Mesenchymal stem cells; Paracrine signalling; Pattern recognition receptors; Phenotypes; Population; Proteins; Senescence; senescence-associated secretory phenotype; small cell; Stem cells; TLR2 protein; TLR5 protein; Toll-like receptors; Umbilical cord; United States > US; Grand Island New York; mesenchymal stem cell senescence; toll-like receptor 5; growth-regulated oncogene-alpha; cell-based therapy; interukin-8; C-X-C motif chemokine receptor 2; senescence-associated secretory phenotype; small cell; toll-like receptor 2
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10010063

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.