Adipose-Derived Stem Cells Can Abrogate Chemical-Induced Liver Fibrosis and Facilitate Recovery of Liver Function
Adipose-Derived Stem Cells Can Abrogate Chemical-Induced Liver Fibrosis and Facilitate Recovery of Liver Function
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DOI：
10.3727/096368912x652959
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发表时间：
2012-01-01
影响因子：
3.3
通讯作者：
Chiou, Tzyy-Wen
中科院分区：
文献类型：
--
作者：
Harn, Horng-Jyh;Lin, Shinn-Zong;Chiou, Tzyy-Wen
脂肪源性干细胞（ADSC）易于收获，并具有自我更新和分化为各种细胞类型（包括肝谱系细胞）的能力。然而，关于脂肪干细胞用于肝移植的研究是有限的。本研究的目的是调查使用人脂肪干细胞的可行性，并更好地了解他们的作用机制，在硫代乙酰胺（TAA）诱导的慢性肝损伤模型的大鼠肝损伤的修复。Wistar大鼠腹腔注射TAA 200 mg/kg，每3 d 1次，共60 d，诱导肝损伤。对于细胞治疗，通过直接肝脏注射将悬浮在300 μ l磷酸盐缓冲盐水中的1 × 10（6）人ADSC移植到每只实验大鼠中。免疫组织化学显示，移植后1周，移植的ADSC分化为分泌白蛋白和甲胎蛋白的肝脏样细胞。此外，通过分析总胆红素、凝血酶原时间和白蛋白水平的生化分析确定肝功能显著恢复。来自组织病理学分析的Metavir评分也显示ADSC移植后肝纤维化和炎症活性显著降低。最后，我们发现，在ADSC移植后，α-平滑肌肌动蛋白（肝星状细胞的标志物，其产生胶原纤维）的表达减少，基质金属蛋白酶-9（降解胶原纤维）的表达增加。这些发现与ADSC治疗组中肝纤维化的消除一致。因此，这些结果表明，ADSC移植可以促进慢性肝损伤的恢复，因此可能具有临床应用价值。
Adipose-derived stem cells (ADSCs) are easy to harvest and have the ability for self-renewal and to differentiate into various cell types, including those of the hepatic lineage. Studies on the use of ADSCs for liver transplantation are, however, limited. The objective of this study was to investigate the feasibility of using human ADSCs and to better understand their mechanism of action for the repair of liver damage in a thioacetamide (TAA)-induced model of chronic liver damage in the rat. To induce liver damage, 200 mg/kg TAA was injected intraperitoneally into Wistar rats every 3 days for 60 days. For cell therapy, 1 x 10(6) human ADSCs suspended in 300 mu l of phosphate-buffered saline were transplanted into each experimental rat by direct liver injection. Immunohistochemistry showed that the transplanted ADSCs differentiated into albumin- and alpha-fetoprotein-secreting liver-like cells 1 week after transplantation. In addition, liver function recovered significantly, as determined by biochemical analyses that analyzed total bilirubin, prothrombin time, and albumin levels. The Metavir score, derived from histopathological analysis, also showed a significant decrease in liver fibrosis and inflammatory activity after ADSC transplantation. Finally, we found a reduction in the expression of alpha-smooth muscle actin, a marker of hepatic stellate cells, which produce collagen fiber, and an increase in the expression of matrix metalloproteinase-9, which degrades collagen fiber, after ADSC transplantation. These findings are consistent with abrogation of liver fibrosis in the ADSC therapy group. Consequently, these results suggest that ADSC transplantation may facilitate recovery from chronic liver damage and thus may have clinical applications.