title: Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment.
abstract: Cardiosphere-derived cells (CDCs), one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1) into a regulatory anti-inflammatory phenotype (M2). Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control. Immunostaining showed that CDCs-conditioned medium significantly enhanced the expression of CD206 (a marker for M2 macrophages), but decreased the expression of CD86 (a marker for M1 macrophages) 3 days after culture. For animal studies, we used an acute myocardial infarction model of mice. We injected CDCs, fibroblasts, or saline only into the border zone of infarction. Then we collected the heart tissues for histological analysis 5 and 14 days after treatment. Compared with control animals, CDCs treatment significantly decreased M1 macrophages and neutrophils but increased M2 macrophages in the infarcted heart. Furthermore, CDCs-treated mice had reduced infarct size and fewer apoptotic cells compared to the controls. Our data suggest that CDCs facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment, which may provide a new insight into the mechanisms of stem cell-based myocardial repair.
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|Department of Medical Pharmacology, Qena Faculty of Medicine, South Valley University, Qena, Egypt.
authors.forename: Al Shaimaa
authors.initials: AS
authors.lastname: Hasan
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tian-Xia
authors.initials: TX
authors.lastname: Zhang
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yoshishige
authors.initials: Y
authors.lastname: Urata
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Goto
authors.affiliation: Department of Medical Pharmacology, Qena Faculty of Medicine, South Valley University, Qena, Egypt.
authors.forename: Safwat A
authors.initials: SA
authors.lastname: Mangoura
authors.affiliation: Department of Medical Pharmacology, Qena Faculty of Medicine, South Valley University, Qena, Egypt.
authors.forename: Mahmoud H
authors.initials: MH
authors.lastname: Abdel-Raheem
authors.affiliation: Department of General Surgery, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi, China.
authors.forename: Shouhua
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Stem Cell Biology, Atomic Bomb Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006321:Heart / Q000502:physiology; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D012038:Regeneration
chemical_list: D051940:B7-2 Antigen; D017077:Culture Media, Conditioned; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface