title: Mesenchymal stem cell-loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium.
abstract: Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF-1α, Tβ4, VEGF and SDF-1 expression and decreased CXCL14 expression in hypoxic and serum-deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF-1α, Tβ4, VEGF, SDF-1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial-derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c-kit+cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c-kit+cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai, China.
authors.forename: Qiang-Li
authors.initials: QL
authors.lastname: Wang
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai, China.
authors.forename: Hai-Jie
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai, China.
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai, China.
authors.forename: Xue-Ping
authors.initials: XP
authors.lastname: Wu
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai, China.
authors.forename: Yu-Zhen
authors.initials: YZ
authors.lastname: Tan
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002196:Capillaries / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D018925:Chemokines / Q000378:metabolism; D019610:Cytoprotection; D005780:Gelatin / Q000737:chemistry; D005786:Gene Expression Regulation; D006334:Heart Function Tests; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D042583:Lymphangiogenesis / Q000235:genetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000648:ultrastructure; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D018919:Neovascularization, Physiologic; D011091:Polyesters / Q000737:chemistry; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013947:Thymosin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099201:Thymosin beta(4)
chemical_list: D001672:Biocompatible Materials; D018925:Chemokines; D005780:Gelatin; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011091:Polyesters; D019009:Proto-Oncogene Proteins c-kit; D013947:Thymosin; D042461:Vascular Endothelial Growth Factor A; D000099201:Thymosin beta(4); C016240:polycaprolactone
keywords: cardiac patch; epicardial-derived cells; epicardium; mesenchymal stem cells; myocardial infarction; myocardial repair