title: Passage-restricted differentiation potential of mesenchymal stem cells into cardiomyocyte-like cells.
abstract: Mesenchymal stem cells (MSCs) have limited ability to differentiate into cardiomyocytes and the factors affect this process are not fully understood. In this study, we investigated the passage (P)-related transdifferentiation potential of MSCs into cardiomyocyte-like cells and its relationship to the proliferation ability. After 5-azacytidine treatment, only P4 but not P1 and P8 rat bone marrow MSCs (rMSCs) showed formation of myotube and expressed cardiomyocyte-associated markers. The growth property analysis showed P4 rMSCs had a growth-arrest appearance, while P1 and P8 rMSCs displayed an exponential growth pattern. When the rapid proliferation of P1 and P8 rMSCs was inhibited by 5-bromo-2-deoxyuridine, a mitosis inhibitor, only P1, not P8 rMSCs, differentiated into cardiomyocyte-like cells after 5-azacytidine treatment. These results demonstrate that the differentiation ability of rMSCs into cardiomyocytes is in proliferation ability-dependent and passage-restricted patterns. These findings reveal a novel regulation on the transdifferentiation of MSCs and provide useful information for exploiting the clinical therapeutic potential of MSCs.
authors.affiliation: Laboratory of Molecular Cardiology and Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), China.
authors.forename: Fa-Bao
authors.initials: FB
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Fang
authors.forename: Ding-Liang
authors.initials: DL
authors.lastname: Zhu
authors.forename: Huang-Tian
authors.initials: HT
authors.lastname: Yang
authors.forename: Ping-Jin
authors.initials: PJ
authors.lastname: Gao
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D001374:Azacitidine