title: Combination of IGF‑1 gene manipulation and 5‑AZA treatment promotes differentiation of mesenchymal stem cells into cardiomyocyte‑like cells.
abstract: Mesenchymal stem cell (MSC) transplantation has been proposed as a promising therapeutic strategy for ischemic myocardium repair following myocardial infarction. Differentiation of MSCs into cardiomyocyte‑like cells prior to cell transplantation is advantageous in improving their potential clinical benefits for cardiac repair. In the present study, we isolated and cultured porcine MSCs and evaluated the synergistic effect of 5‑azacytidine (5‑AZA) treatment and insulin‑like growth factor‑1 (IGF‑1) gene manipulation on MSC differentiation into cardiomyocyte‑like cells. Our results demonstrated that 5‑AZA treatment alone induced a limited cardiomyocyte‑like differentiation effect in vitro. Overexpression of the IGF‑1 gene in MSCs improved the induction effect of 5‑AZA, while knockdown of the IGF‑1 gene attenuated the differentiation. These results suggest that IGF‑1 is a significant stimulus affecting the cardiomyocyte‑like differentiation of porcine MSCs. In addition, the combination of IGF‑1 gene manipulation and 5‑AZA treatment provides a new strategy to obtain more committed differentiated cardiomyocyte‑like cells from porcine MSCs prior to cell transplantation.
authors.affiliation: Department of Cardiac Surgery, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiac Surgery, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhu
authors.affiliation: Department of Cardiac Surgery, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiac Surgery, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Cardiac Surgery, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Changfa
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Cardiac Surgery, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Lai
authors.affiliation: Department of Cardiac Surgery, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013552:Swine
chemical_list: D034741:RNA, Small Interfering; D007334:Insulin-Like Growth Factor I; D001374:Azacitidine