Inflammatory Cytokines Alter Mesenchymal Stem Cell Mechanosensing and Adhesion on Stiffened Infarct Heart Tissue After Myocardial Infarction
Mesenchymal stem cell (MSC) transplantation has demonstrated its potential in repairing infarct heart tissue and recovering heart function after myocardial infarction (MI). However, its therapeutic effect is still limited due to poor MSC engraftment at the injury site whose tissue stiffness and loca...
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| Format: | Article |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.583700/full |
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| author | Dan Zhu Peng Wu Peng Wu Changchen Xiao Wei Hu Tongtong Zhang Xinyang Hu Wei Chen Wei Chen Jian’an Wang |
| author_facet | Dan Zhu Peng Wu Peng Wu Changchen Xiao Wei Hu Tongtong Zhang Xinyang Hu Wei Chen Wei Chen Jian’an Wang |
| author_sort | Dan Zhu |
| collection | DOAJ |
| description | Mesenchymal stem cell (MSC) transplantation has demonstrated its potential in repairing infarct heart tissue and recovering heart function after myocardial infarction (MI). However, its therapeutic effect is still limited due to poor MSC engraftment at the injury site whose tissue stiffness and local inflammation both dynamically and rapidly change after MI. Whether and how inflammatory cytokines could couple with stiffness change to affect MSC engraftment in the infarct zone still remain unclear. In this study, we characterized dynamic stiffness changes of and inflammatory cytokine expression in the infarct region of rat heart within a month after MI. We found that the tissue stiffness of the heart tissue gradually increased and peaked 21 days after MI along with the rapid upregulation of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the first 3 days, followed by a sharp decline. We further demonstrated in vitro that immobilized inflammatory cytokine IL-6 performed better than the soluble form in enhancing MSC adhesion to stiffened substrate through IL-6/src homology 2 (SH2) domain-containing tyrosine phosphatase-2 (SHP2)/integrin signaling axis. We also confirmed such mechano-immune coupling of tissue stiffness and inflammatory cytokines in modulating MSC engraftment in the rat heart after MI in vivo. Our study provides new mechanistic insights of mechanical–inflammation coupling to improve MSC mechanosensing and adhesion, potentially benefiting MSC engraftment and its clinical therapy for MI. |
| first_indexed | 2024-04-13T14:20:07Z |
| format | Article |
| id | doaj.art-b5563ee7817b42689260e52879975dee |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-13T14:20:07Z |
| publishDate | 2020-10-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-b5563ee7817b42689260e52879975dee2022-12-22T02:43:31ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-10-01810.3389/fcell.2020.583700583700Inflammatory Cytokines Alter Mesenchymal Stem Cell Mechanosensing and Adhesion on Stiffened Infarct Heart Tissue After Myocardial InfarctionDan Zhu0Peng Wu1Peng Wu2Changchen Xiao3Wei Hu4Tongtong Zhang5Xinyang Hu6Wei Chen7Wei Chen8Jian’an Wang9Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Pharmacology, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory for Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, ChinaKey Laboratory for Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, ChinaDepartment of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaKey Laboratory for Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, ChinaDepartment of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaMesenchymal stem cell (MSC) transplantation has demonstrated its potential in repairing infarct heart tissue and recovering heart function after myocardial infarction (MI). However, its therapeutic effect is still limited due to poor MSC engraftment at the injury site whose tissue stiffness and local inflammation both dynamically and rapidly change after MI. Whether and how inflammatory cytokines could couple with stiffness change to affect MSC engraftment in the infarct zone still remain unclear. In this study, we characterized dynamic stiffness changes of and inflammatory cytokine expression in the infarct region of rat heart within a month after MI. We found that the tissue stiffness of the heart tissue gradually increased and peaked 21 days after MI along with the rapid upregulation of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the first 3 days, followed by a sharp decline. We further demonstrated in vitro that immobilized inflammatory cytokine IL-6 performed better than the soluble form in enhancing MSC adhesion to stiffened substrate through IL-6/src homology 2 (SH2) domain-containing tyrosine phosphatase-2 (SHP2)/integrin signaling axis. We also confirmed such mechano-immune coupling of tissue stiffness and inflammatory cytokines in modulating MSC engraftment in the rat heart after MI in vivo. Our study provides new mechanistic insights of mechanical–inflammation coupling to improve MSC mechanosensing and adhesion, potentially benefiting MSC engraftment and its clinical therapy for MI.https://www.frontiersin.org/articles/10.3389/fcell.2020.583700/fullcytokinemechanosensingadhesionmesenchymal stem cellmyocardial infarction |
| spellingShingle | Dan Zhu Peng Wu Peng Wu Changchen Xiao Wei Hu Tongtong Zhang Xinyang Hu Wei Chen Wei Chen Jian’an Wang Inflammatory Cytokines Alter Mesenchymal Stem Cell Mechanosensing and Adhesion on Stiffened Infarct Heart Tissue After Myocardial Infarction Frontiers in Cell and Developmental Biology cytokine mechanosensing adhesion mesenchymal stem cell myocardial infarction |
| title | Inflammatory Cytokines Alter Mesenchymal Stem Cell Mechanosensing and Adhesion on Stiffened Infarct Heart Tissue After Myocardial Infarction |
| title_full | Inflammatory Cytokines Alter Mesenchymal Stem Cell Mechanosensing and Adhesion on Stiffened Infarct Heart Tissue After Myocardial Infarction |
| title_fullStr | Inflammatory Cytokines Alter Mesenchymal Stem Cell Mechanosensing and Adhesion on Stiffened Infarct Heart Tissue After Myocardial Infarction |
| title_full_unstemmed | Inflammatory Cytokines Alter Mesenchymal Stem Cell Mechanosensing and Adhesion on Stiffened Infarct Heart Tissue After Myocardial Infarction |
| title_short | Inflammatory Cytokines Alter Mesenchymal Stem Cell Mechanosensing and Adhesion on Stiffened Infarct Heart Tissue After Myocardial Infarction |
| title_sort | inflammatory cytokines alter mesenchymal stem cell mechanosensing and adhesion on stiffened infarct heart tissue after myocardial infarction |
| topic | cytokine mechanosensing adhesion mesenchymal stem cell myocardial infarction |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2020.583700/full |
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