title: Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis.
abstract: OBJECTIVE
  Therapies involving bone-marrow-derived mesenchymal stem cells (BM-MSCs) have considerable potential in the management of hepatic disease. BM-MSCs have been investigated in regenerative medicine due to their ability to secrete various growth factors and cytokines that regress hepatic fibrosis and enhance hepatocyte functionality. The aim of this study was to determine the antifibrosis effect of BM-MSCs on activated hepatic stellate cells (HSCs) and the mechanism underlying how BM-MSCs modulate the function of activated HSCs.
  
  
  METHODS
  We used HSCs in both direct and indirect co-culture systems with BM-MSCs to evaluate the antifibrosis effect of BM-MSCs. The cell viability and apoptosis were evaluated by a direct co-culture system of activated HSCs with BM-MSCs. The activations of both HSCs alone and HSCs with BM-MSCs in the direct co-culture system were observed by immunocytochemistry for alpha-smooth muscle actin (α-SMA). The levels of growth factors and cytokines were evaluated by an indirect co-culture system of activated HSCs with BM-MSCs.
  
  
  RESULTS
  The BM-MSCs in the direct co-culture system significantly decreased the production of α-SMA and the viability of activated HSCs, whereas they induced the apoptosis of activated HSCs. The BM-MSCs in the indirect co-culture system decreased the production of transforming growth factor-β1 and interleukin (IL)-6, whereas they increased the production of hepatocyte growth factor and IL-10. These results confirmed that the juxtacrine and paracrine effects of BM-MSCs can inhibit the proliferative, fibrogenic function of activated HSCs and have the potential to reverse the fibrotic process by inhibiting the production of α-SMA and inducing the apoptosis of HSCs.
  
  
  CONCLUSIONS
  These results have demonstrated that BM-MSCs may exert an antifibrosis effect by modulating the function of activated HSCs.
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. ; Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Yoon Ok
authors.initials: YO
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Baek Gyu
authors.initials: BG
authors.lastname: Jun
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. ; Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Sang Ok
authors.initials: SO
authors.lastname: Kwon
mesh_terms: D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D018920:Coculture Techniques; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008103:Liver Cirrhosis; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D017228:Hepatocyte Growth Factor
keywords: Bone-marrow-derived mesenchymal stem cell; Cirrhosis; Hepatic fibrosis