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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Published in | Cells (Basel, Switzerland) Vol. 10; no. 1; p. 63 |
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Main Authors | , , , , , , , , |
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Abstract | 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. |
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AbstractList | 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. |
Author | Kwon, Ji Hye Bae, Yun Kyung Jin, Hye Jin Kim, Miyeon Lee, Hyang Ju Choi, Soo Jin Hwang, Hyun Ho Um, Soyoun Oh, Wonil |
AuthorAffiliation | 2 King Abdullah University of Science and Technology, Thuwal 47000, Makkah Province, Saudi Arabia; heno.hwang@kaust.edu.sa 1 Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea; kjh0127@medi-post.co.kr (J.H.K.); eldjfls3@medi-post.co.kr (M.K.); ssoso23@medi-post.co.kr (S.U.); hjlee@medi-post.co.kr (H.J.L.); byk819@medi-post.co.kr (Y.K.B.); sjchoi@medi-post.co.kr (S.J.C.); wioh@medi-post.co.kr (W.O.) |
AuthorAffiliation_xml | – name: 1 Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea; kjh0127@medi-post.co.kr (J.H.K.); eldjfls3@medi-post.co.kr (M.K.); ssoso23@medi-post.co.kr (S.U.); hjlee@medi-post.co.kr (H.J.L.); byk819@medi-post.co.kr (Y.K.B.); sjchoi@medi-post.co.kr (S.J.C.); wioh@medi-post.co.kr (W.O.) – name: 2 King Abdullah University of Science and Technology, Thuwal 47000, Makkah Province, Saudi Arabia; heno.hwang@kaust.edu.sa |
Author_xml | – sequence: 1 givenname: Ji Hye surname: Kwon fullname: Kwon, Ji Hye organization: Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea – sequence: 2 givenname: Miyeon orcidid: 0000-0003-0497-8148 surname: Kim fullname: Kim, Miyeon organization: Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea – sequence: 3 givenname: Soyoun orcidid: 0000-0003-0034-114X surname: Um fullname: Um, Soyoun organization: Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea – sequence: 4 givenname: Hyang Ju surname: Lee fullname: Lee, Hyang Ju organization: Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea – sequence: 5 givenname: Yun Kyung surname: Bae fullname: Bae, Yun Kyung organization: Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea – sequence: 6 givenname: Soo Jin surname: Choi fullname: Choi, Soo Jin organization: Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea – sequence: 7 givenname: Hyun Ho orcidid: 0000-0002-0011-7845 surname: Hwang fullname: Hwang, Hyun Ho organization: King Abdullah University of Science and Technology, Thuwal 47000, Makkah Province, Saudi Arabia – sequence: 8 givenname: Wonil surname: Oh fullname: Oh, Wonil organization: Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea – sequence: 9 givenname: Hye Jin surname: Jin fullname: Jin, Hye Jin organization: Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea |
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Keywords | 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 |
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SubjectTerms | 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 |
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Title | Senescence-Associated Secretory Phenotype Suppression Mediated by Small-Sized Mesenchymal Stem Cells Delays Cellular Senescence through TLR2 and TLR5 Signaling |
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