title: Anti-fibrotic effect of chorionic plate-derived mesenchymal stem cells isolated from human placenta in a rat model of CCl(4)-injured liver: potential application to the treatment of hepatic diseases.
abstract: Translational studies have explored the therapeutic effects of stem cells, raising hopes for the treatment of numerous diseases. Here, we evaluated the therapeutic effect of chorionic plate-derived mesenchymal stem cells (CP-MSCs) isolated from human placenta and transplanted into rats with carbon tetrachloride (CCl(4))-injured livers. CP-MSCs were analyzed for hepatocyte-specific gene expression, indocyanine green (ICG) uptake, glycogen storage, and urea production following hepatogenic differentiation. PKH26-labeled CP-MSCs were directly transplanted into the livers of rats that had been exposed to CCl(4) (1.6 g/kg, twice per week for 9 weeks). Blood and liver tissue were analyzed at 1, 2, and 3 weeks post-transplantation. The expression of type I collagen (Col I) and matrix metalloproteinases (MMPs) was analyzed in rat T-HSC/Cl-6 hepatic stellate cells co-cultured with CP-MSCs following exposure to TGF-β. The expression levels of α-smooth muscle actin (α-SMA) and Col I were lower in transplanted (TP) rats than in non-transplanted (Non-TP) animals (P < 0.05), whereas the expression levels of albumin and MMP-9 were increased. TP rats exhibited significantly higher uptake/excretion of ICG than non-TP rats (P < 0.005). In addition, collagen synthesis in T-HSC/Cl-6 cells exposed to TGF-β was decreased by co-culture with CP-MSCs, which triggered the activation of MMP-2 and MMP-9. These results contribute to our understanding of the potential pathophysiological roles of CP-MSCs, including anti-fibrotic effects in liver disease, and provide a foundation for the development of new cell therapy-based strategies for the treatment of difficult-to-treat liver diseases.
authors.affiliation: School of Veterinary Medicine, Kangwon National University, Chuncheon, Kangwon-do, Republic of Korea.
authors.forename: Min-Jae
authors.initials: MJ
authors.lastname: Lee
authors.forename: Jieun
authors.initials: J
authors.lastname: Jung
authors.forename: Kyu-Hwan
authors.initials: KH
authors.lastname: Na
authors.forename: Ji Suk
authors.initials: JS
authors.lastname: Moon
authors.forename: Hey-Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: Kim
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kwon
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Hwang
authors.forename: Gi Jin
authors.initials: GJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D016212:Transforming Growth Factor beta; D002251:Carbon Tetrachloride