title: Effect of bone marrow-derived mesenchymal stem cells on hepatic fibrosis in a thioacetamide-induced cirrhotic rat model.
abstract: BACKGROUND
  Cirrhosis is a long-term consequence of chronic hepatic injury with fibrosis. No effective therapy is currently available for decompensated cirrhosis except liver transplantation. Hence, we investigated the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on hepatic fibrosis in a thioacetamide (TAA)-induced cirrhotic rat model.
  
  
  METHODS
  The BM-MSCs were injected directly into the right liver lobe twice, at 6 and 8 weeks during the 12-week TAA administration, in thioacetamide (TAA)-induced cirrhotic rats model, and hepatic fibrosis was evaluated. At 12 weeks, the effect of BM-MSCs on hepatic fibrosis was analyzed histomorphologically using the Laennec fibrosis scoring system, and the collagen proportionate area was quantified. Cirrhosis-related factors, such as transforming growth factor β1 (TGF-β1), type 1 collagen (collagen-1), α-smooth muscle actin (α-SMA), and P-Smad3/Smad3 expression levels, were evaluated using real-time polymerase chain reaction and western blot assays.
  
  
  RESULTS
  According to the Laennec fibrosis scoring system, histological improvement was observed in hepatic fibrosis after BM-MSC treatment (P <0.01). The percentage of the collagen proportionate area decreased from 16.72 ± 5.51 to 5.06 ± 1.27 after BM-MSC treatment (P <0.01). The content of hepatic hydroxyproline was significantly lower in the BM-MSC treated group (46.25 ± 13.19) compared to the untreated cirrhotic group (85.81 ± 17.62; P <0.01). BM-MSC administration significantly decreased TGF-β1, collagen-1, and α-SMA expression in TAA-induced cirrhotic rats (P <0.01). We also confirmed P-Smad3/Smad3, downstream effectors of the TGF-β1 signaling pathway, and found that MSC transplantation inhibited Smad3 phosphorylation.
  
  
  CONCLUSIONS
  BM-MSC treatment attenuated hepatic fibrosis in rats with TAA-induced cirrhosis, raising the possibility of the clinical use of BM-MSCs in the treatment of cirrhosis.
authors.affiliation: Department of Internal Medicine, Yonsei University, Wonju College of Medicine, 162, Ilsan-dong, Wonju, Republic of Korea. jangyo@yonsei.ac.kr.
authors.forename: Yoon Ok
authors.initials: YO
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Yonsei University, Wonju College of Medicine, 162, Ilsan-dong, Wonju, Republic of Korea. drkimmy@yonsei.ac.kr.
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University, Wonju College of Medicine, 162, Ilsan-dong, Wonju, Republic of Korea. meeyon@yonsei.ac.kr.
authors.forename: Mee Yon
authors.initials: MY
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Yonsei University, Wonju College of Medicine, 162, Ilsan-dong, Wonju, Republic of Korea. baiksk@yonsei.ac.kr.
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
authors.affiliation: Department of Internal Medicine, Yonsei University, Wonju College of Medicine, 162, Ilsan-dong, Wonju, Republic of Korea. youn07190720@naver.com.
authors.forename: Youn Zoo
authors.initials: YZ
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Yonsei University, Wonju College of Medicine, 162, Ilsan-dong, Wonju, Republic of Korea. sangokkwon@yonsei.ac.kr.
authors.forename: Sang Ok
authors.initials: SO
authors.lastname: Kwon
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000145:classification; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000199:Actins; D024042:Collagen Type I; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D012333:RNA, Messenger; D013853:Thioacetamide; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; C498862:Acta2 protein, rat