Mesenchymal stem cells attenuate cardiac fibroblast proliferation and collagen synthesis through paracrine actions.

Mesenchymal stem cells (MSC) transplantation has been shown to decrease fibrosis in the heart; however, whether MSC directly influence the function of cardiac fibroblasts (CFB) remains unknown. MSC-conditioned medium significantly attenuated proliferation of CFB compared with CFB-conditioned medium. MSC-conditioned medium upregulated antiproliferation-related genes such as elastin, myocardin and DNA-damage inducible transcript 3, whereas CFB-conditioned medium upregulated proliferation-related genes such as alpha-2-macroglobulin and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog. MSC-conditioned medium significantly downregulated type I and III collagen expression, and significantly suppressed type III collagen promoter activity. MSC may exert paracrine anti-fibrotic effects at least in part through regulation of CFB proliferation and collagen synthesis.