Paracrine action mediate the antifibrotic effect of transplanted mesenchymal stem cells in a rat model of global heart failure.
OBJECTIVE
We aimed to investigate the mechanism mediating the antifibrotic effects of mesenchymal stem cells (MSCs) via in vitro and in vivo study.


METHODS
In vitro, cardiac fibroblasts (CFs) from passage 2 were cultured and incubated with DMEM/F12 supplemented with 10% fetal bovine serum (DM-10), DM-10 containing angiotensin II (Ang II, 1 x 10(-6) M) or a combination of MSC-conditioned medium (MSC-CM) and Ang II (1 x 10(-6) M) for 48 h. CFs proliferation and gene expression of collagen I and III were analyzed by MTT and reverse transcription-polymerase chain reaction (RT-PCR). In vivo, global heart failure was induced in Wistar rats by isoproterenol (ISO) injection. Four weeks later, MSCs or culture medium were transplanted by intramyocardial injection. Four weeks after transplantation, heart function was assessed, and histological analysis conducted. In addition, the expression of adrenomedullin (ADM), an antifibrotic factor, in MSCs and myocardium were also examined.


RESULTS
In vitro, MSCs expressed ADM. MSC-CM obviously inhibited CFs proliferation and expression of collagen I and III mRNA. In vivo, compared with medium transplantation, MSC transplantation significantly improved heart function, decreased collagen volume fraction and increased expression of ADM in myocardium.


CONCLUSIONS
MSC transplantation can inhibit function of CFs by secreting antifibrotic factors such as ADM, resulting in decrease of myocardial fibrosis.
Li
Lili
L
Department of Cardiology, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, P.R. China, lisister1980@163.com.
Zhang
Shuo
S
Zhang
Yao
Y
Yu
Bo
B
Xu
Yan
Y
Guan
Zhenzhong
Z
D053607:Adrenomedullin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D048430:Cell Shape; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D019899:Paracrine Communication; D051381:Rats; D017208:Rats, Wistar
D053607:Adrenomedullin