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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MDPI AG
2021-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/1/63 |
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| author | Ji Hye Kwon Miyeon Kim Soyoun Um Hyang Ju Lee Yun Kyung Bae Soo Jin Choi Hyun Ho Hwang Wonil Oh Hye Jin Jin |
| author_facet | Ji Hye Kwon Miyeon Kim Soyoun Um Hyang Ju Lee Yun Kyung Bae Soo Jin Choi Hyun Ho Hwang Wonil Oh Hye Jin Jin |
| author_sort | Ji Hye Kwon |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T13:32:14Z |
| format | Article |
| id | doaj.art-bcd0421e81d645c8b0e56b06b330b5bc |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T13:32:14Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-bcd0421e81d645c8b0e56b06b330b5bc2023-11-21T07:55:27ZengMDPI AGCells2073-44092021-01-011016310.3390/cells10010063Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 SignalingJi Hye Kwon0Miyeon Kim1Soyoun Um2Hyang Ju Lee3Yun Kyung Bae4Soo Jin Choi5Hyun Ho Hwang6Wonil Oh7Hye Jin Jin8Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaKing Abdullah University of Science and Technology, Thuwal 47000, Makkah Province, Saudi ArabiaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, KoreaIn 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.https://www.mdpi.com/2073-4409/10/1/63small cellmesenchymal stem cell senescencesenescence-associated secretory phenotypegrowth-regulated oncogene-alphainterukin-8C-X-C motif chemokine receptor 2 |
| spellingShingle | Ji Hye Kwon Miyeon Kim Soyoun Um Hyang Ju Lee Yun Kyung Bae Soo Jin Choi Hyun Ho Hwang Wonil Oh Hye Jin Jin Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling Cells small cell mesenchymal stem cell senescence senescence-associated secretory phenotype growth-regulated oncogene-alpha interukin-8 C-X-C motif chemokine receptor 2 |
| 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 | small cell mesenchymal stem cell senescence senescence-associated secretory phenotype growth-regulated oncogene-alpha interukin-8 C-X-C motif chemokine receptor 2 |
| url | https://www.mdpi.com/2073-4409/10/1/63 |
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