%0 Journal Article
%T Effect of Mesenchymal Stem Cells on Doxorubicin-Induced Fibrosis
%A Simin Mohammadi Gorji
%A Abbas Ali Karimpor Malekshah
%A Mohammad Baghere Hashemi-Soteh
%A Alireza Rafiei
%J Cell Journal
%D 2012
%I Royan Institute (ACECR), Tehran
%X Objective: The aim of this study was to test the effect of intravenous injection of mesenchymal stem cells (MSCs) on doxorubicin (DOX)-induced fibrosis in the heart. We investigated the mechanisms that possibly mediate this effect.Materials and Methods: In this experimental study, fibrosis in the myocardium of adult male Wistar rats (weights 180-200 g, 9-10 weeks of age, total n=30) was created by DOX administration. DOX (2.5 mg/kg) was administered intraperitoneally 3 times a week, for a total dose of 15 mg/kg over a period of 2 weeks. MSCs from Wistar rats were separated and cultured in Dulbecco¡¯s modified eagle medium (DMEM). The condition medium (CM) which contained factors secreted by MSCs was also collected from MSCs cultured in serum-free DMEM. Two weeks after the first injection of DOX, MSCs, CM and standard medium (SM) were transplanted via intravenous injection. Four weeks after transplantation, histological (Masson¡¯s trichrome staining for fibrosis detection) and molecular [real-time polymerase chain reaction (RT-PCR)] analyses were conducted. In addition, insulin-like growth factor (IGF-1) and hepatocyte growth factor (HGF) in the CM were measured with an enzyme-linked immunosorbent assay (ELISA). For immunosuppressive treatment, cyclosporine A was given (intraperitoneally, 5 mg/kg/day) starting on the day of surgery until the end of study in all groups. Fibrosis rate and relative gene expression were compared by analysis of variance (ANOVA) and post-Tukey¡¯s test. HGF and (IGF-1 in the CM were analyzed by independent sample t test. P<0.01 was considered statistically significant.Results: Our data demonstrated that intravenously transplanted MSCs and CM significantly reduced fibrosis and significantly increased Bcl-2 expression levels in the myocardium compared to the DOX group (p<0.01). However, there was no significant difference between Bax expression levels in these groups. In addition, secretion of HGF and IGF-1 was detected in the CM (p<0.01).Conclusion: We conclude that intravenous transplantation of MSCs and CM can attenuate myocardial fibrosis and increase Bcl-2 expression. This may be mediated by paracrine signaling from MSCs via anti-fibrotic and anti-apoptotic factors such as HGF and IGF-1.
%K Mesenchymal Stem Cell
%K Doxorubicin
%K Heart
%K Apoptosis
%K Fibrosis
%U http://celljournal.org/library/upload/article/af_2284335225237336223226646554262278225254gorji.pdf