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- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2014.1
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Bone marrow-derived mesenchymal stromal cells (MSCs) have been reported to be beneficial for the treatment of liver fibrosis. Here, we investigated the use of genetically engineered MSCs that overexpress hepatocyte growth factor (HGF) as a means to improve their therapeutic effect in liver fibrosis. Liver fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. HGF-secreting MSCs (MSCs/HGF) were prepared by transducing MSCs with an adenovirus carrying HGF-encoding cDNA. MSCsor MSCs/HGF were injected directly into the spleen of fibrotic rats. Tissue fibrosis was assessed by histological analysis 12 days after stem cell injection. Although treatment with MSCs reduced fibrosis, treatment with MSCs/HGF produced a more significant reduction and was associated with elevated HGF levels in the portal vein. Collagen levels in the liver extract were decreased after MSC/HGF therapy, suggesting recovery from fibrosis. Furthermore, liver function was improved in animalsreceiving MSCs/HGF, indicating that MSC/HGF therapy resulted not only in reduction of liver fibrosis but also in improvement of hepatocyte function. Assessment of cell and biochemical parameters revealed that mRNA levels of the fibrogenic cytokines PDGF-bb and TGF-b1 were significantly decreased after MSC/HGF therapy. Subsequent to the decrease in collagen, expression of matrix metalloprotease-9 (MMP-9), MMP-13, MMP-14 and urokinase-type plasminogen activator was augmented following MSC/HGF, whereas tissue inhibitor of metalloprotease-1 (TIMP-1) expression was reduced. In conclusion, therapy with MSCs/HGF resulted in an improved therapeutic effect compared with MSCs alone, probably because of the anti-fibrotic activity of HGF. Thus, MSC/HGF represents a promising approach toward a cell therapy for liver fibrosis.
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참고문헌 (25)
참고문헌 신청
Balkovetz DF / 1998 / Hepatocyte growth factor and Madin-Darby canine kidney cells : in vitro models of epithelial cell movement and morphogenesis / Microsc Res Tech 43 : 45
Bataller R / 2005 / Liver fibrosis / J Clin Invest 115 : 209 ~ 218
Carvalho AB / 2008 / Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury / Stem Cells 2
Edwards CA / 1980 / Modified assay for determination of hydroxyproline in a tissue hydrolyzate / Clin Chim Acta 104 : 161 ~ 167
Fang B / 2004 / Systemic infusion of FLK1(þ)mesenchymal stem cells ameliorate carbon tetrachlorideinduced liver fibrosis in mice / Transplantation 78 : 83 ~ 88
Bataller R / 2005 / Liver fibrosis / J Clin Invest 115 : 209 ~ 218
Carvalho AB / 2008 / Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury / Stem Cells 2
Edwards CA / 1980 / Modified assay for determination of hydroxyproline in a tissue hydrolyzate / Clin Chim Acta 104 : 161 ~ 167
Fang B / 2004 / Systemic infusion of FLK1(þ)mesenchymal stem cells ameliorate carbon tetrachlorideinduced liver fibrosis in mice / Transplantation 78 : 83 ~ 88
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