Cardiac Nestin+ Mesenchymal Stromal Cells Enhance Healing of Ischemic Heart through Periostin-Mediated M2 Macrophage Polarization
| Autor: | Chaoquan Peng, Yang Chen, Yan Liao, Mei Hua Jiang, Andy Peng Xiang, Xiaoran Zhang, Maosheng Wang, Gang Dai, Weijun Huang, Zhihong Chen, Guilan Li, Dihan Lu, Junyi Lin, Bingyuan Wu, Dongmei Xie, Xinxin Chen, Zhongyuan Zhang, Shuanghua Zhu, Wanwen Lin |
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| Rok vydání: | 2020 |
| Předmět: |
Cardiac function curve
Genotype Myocardial Ischemia Macrophage polarization Mice Transgenic Periostin Immunophenotyping Nestin Mice 03 medical and health sciences Paracrine signalling 0302 clinical medicine Drug Discovery Genetics Animals Medicine Molecular Biology 030304 developmental biology Pharmacology Wound Healing 0303 health sciences business.industry Macrophages Mesenchymal stem cell Transdifferentiation Cell Differentiation Mesenchymal Stem Cells Macrophage Activation M2 Macrophage Disease Models Animal 030220 oncology & carcinogenesis Cancer research Molecular Medicine Original Article business Cell Adhesion Molecules Biomarkers |
| Zdroj: | Mol Ther |
| ISSN: | 1525-0016 |
| DOI: | 10.1016/j.ymthe.2020.01.011 |
| Popis: | Mesenchymal stromal cells (MSCs) show potential for treating cardiovascular diseases, but their therapeutic efficacy exhibits significant heterogeneity depending on the tissue of origin. This study sought to identify an optimal source of MSCs for cardiovascular disease therapy. We demonstrated that Nestin was a suitable marker for cardiac MSCs (Nes(+)cMSCs), which were identified by their self-renewal ability, tri-lineage differentiation potential, and expression of MSC markers. Furthermore, compared with bone marrow-derived MSCs (Nes(+)bmMSCs) or saline-treated myocardial infarction (MI) controls, intramyocardial injection of Nes(+)cMSCs significantly improved cardiac function and decreased infarct size after acute MI (AMI) through paracrine actions, rather than transdifferentiation into cardiac cells in infarcted heart. We further revealed that Nes(+)cMSC treatment notably reduced pan-macrophage infiltration while inducing macrophages toward an anti-inflammatory M2 phenotype in ischemic myocardium. Interestingly, Periostin, which was highly expressed in Nes(+)cMSCs, could promote the polarization of M2-subtype macrophages, and knockdown or neutralization of Periostin remarkably reduced the therapeutic effects of Nes(+)cMSCs by decreasing M2 macrophages at lesion sites. Thus, the present work systemically shows that Nes(+)cMSCs have greater efficacy than do Nes(+)bmMSCs for cardiac healing after AMI, and that this occurs at least partly through Periostin-mediated M2 macrophage polarization. |
| Databáze: | OpenAIRE |
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