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Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells
Authors:Nakanishi Chiaki  Yamagishi Masakazu  Yamahara Kenichi  Hagino Ikuo  Mori Hidezo  Sawa Yoshiki  Yagihara Toshikatsu  Kitamura Soichiro  Nagaya Noritoshi
Affiliation:a Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
b Division of Cardiovascular Medicine, Kanazawa University, Graduate School of Medicine, Kanazawa, Japan
c Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan
d Department of Cardiac Physiology, National Cardiovascular Center Research Institute, Osaka, Japan
e Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Abstract:Mesenchymal stem cells (MSC) transplantation has been proved to be promising strategy to treat the failing heart. The effect of MSC transplantation is thought to be mediated mainly in a paracrine manner. Recent reports have suggested that cardiac progenitor cells (CPC) reside in the heart. In this study, we investigated whether MSC had paracrine effects on CPC in vitro. CPC were isolated from the neonatal rat heart using an explant method. MSC were isolated from the adult rat bone marrow. MSC-derived conditioned medium promoted proliferation of CPC and inhibited apoptosis of CPC induced by hypoxia and serum starvation. Chemotaxis chamber assay demonstrated that MSC-derived conditioned medium enhanced migration of CPC. Furthermore, MSC-derived conditioned medium upregulated expression of cardiomyocyte-related genes in CPC such as β-myosin heavy chain (β-MHC) and atrial natriuretic peptide (ANP). In conclusion, MSC-derived conditioned medium had protective effects on CPC and enhanced their migration and differentiation.
Keywords:Cardiac progenitor cell   Mesenchymal stem cell   Paracrine effect   Proliferation   Migration   Differentiation
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