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.
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Osaka 565-8565, Japan. sonishi@ri.ncvc.go.jp
Shunsuke
S
Ohnishi
Hideaki
H
Sumiyoshi
Soichiro
S
Kitamura
Noritoshi
N
Nagaya
D000818:Animals; D049109:Cell Proliferation; D024042:Collagen Type I / Q000096:biosynthesis*; D024061:Collagen Type III / Q000096:biosynthesis*; D017077:Culture Media, Conditioned; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006331:Heart Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009124:Muscle Proteins / Q000096:biosynthesis; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication; D011401:Promoter Regions, Genetic; D051381:Rats; D011917:Rats, Inbred Lew; D015854:Up-Regulation
D024042:Collagen Type I; D024061:Collagen Type III; D017077:Culture Media, Conditioned; D009124:Muscle Proteins