Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells.
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 beta-myosin heavy chain (beta-MHC) and atrial natriuretic peptide (ANP). In conclusion, MSC-derived conditioned medium had protective effects on CPC and enhanced their migration and differentiation.
Nakanishi
Chiaki
C
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Yamagishi
Masakazu
M
Yamahara
Kenichi
K
Hagino
Ikuo
I
Mori
Hidezo
H
Sawa
Yoshiki
Y
Yagihara
Toshikatsu
T
Kitamura
Soichiro
S
Nagaya
Noritoshi
N
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002633:Chemotaxis; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015870:Gene Expression; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D032386:Myoblasts, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019899:Paracrine Communication; D051381:Rats; D011917:Rats, Inbred Lew; D015854:Up-Regulation; D024723:Ventricular Myosins / Q000235:genetics
D017077:Culture Media, Conditioned; D009320:Atrial Natriuretic Factor; D024723:Ventricular Myosins