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Mesenchymal stem cell-loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium.
- Source :
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Journal of cellular and molecular medicine [J Cell Mol Med] 2017 Sep; Vol. 21 (9), pp. 1751-1766. Date of Electronic Publication: 2017 Feb 28. - Publication Year :
- 2017
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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 <superscript>+</superscript> 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 <superscript>+</superscript> cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.<br /> (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
- Subjects :
- Animals
Biocompatible Materials chemistry
Capillaries pathology
Cell Differentiation genetics
Cell Survival genetics
Chemokines metabolism
Cytoprotection
Gelatin chemistry
Gene Expression Regulation
Heart Function Tests
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Lymphangiogenesis genetics
Male
Mesenchymal Stem Cells ultrastructure
Mice
Myocardial Infarction physiopathology
Neovascularization, Physiologic
Polyesters chemistry
Proto-Oncogene Proteins c-kit metabolism
Rats, Sprague-Dawley
Thymosin metabolism
Vascular Endothelial Growth Factor A metabolism
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells cytology
Myocardial Infarction pathology
Myocardial Infarction therapy
Myocardium pathology
Regeneration
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 21
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28244640
- Full Text :
- https://doi.org/10.1111/jcmm.13097