Effect of bone marrow-derived mesenchymal stem cells on hepatic fibrosis in a thioacetamide-induced cirrhotic rat model.
Effect of bone marrow-derived mesenchymal stem cells on hepatic fibrosis in a thioacetamide-induced cirrhotic rat model.
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DOI：
10.1186/s12876-014-0198-6
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发表时间：
2014-11-25
影响因子：
2.4
通讯作者：
Kwon SO
中科院分区：
文献类型：
--
作者：
Jang YO;Kim MY;Cho MY;Baik SK;Cho YZ;Kwon SO
肝硬化是慢性肝损伤伴纤维化的长期后果。失代偿期肝硬化除肝移植外，目前尚无有效的治疗方法。因此，我们研究了骨髓间充质干细胞（BM-MSCs）对硫代乙酰胺（TAA）诱导的大鼠肝纤维化模型的影响。在TAA诱导的大鼠肝纤维化模型中，在TAA给药12周期间的第6周和第8周，将BM-MSCs直接注射到右肝叶中两次，并评估肝纤维化。在12周时，使用Laennec纤维化评分系统在组织形态学上分析BM-MSCs对肝纤维化的影响，并量化胶原比例面积。肝硬化相关因子，如转化生长因子β1（TGF-β1），1型胶原（胶原-1），α-平滑肌肌动蛋白（α-SMA）和P-Smad 3/Smad 3表达水平，采用实时聚合酶链反应和蛋白质印迹法进行评价。根据Laennec纤维化评分系统，BM-MSC治疗后肝纤维化组织学明显改善（P <0.01）。骨髓间充质干细胞处理后，胶原比例面积百分比由16.72 ± 5.51降至5.06 ± 1.27（P <0.01）。BM-MSC治疗组肝组织羟脯氨酸含量（46.25 ± 13.19）显著低于未治疗组（85.81 ± 17.62）（P <0.01）。BM-MSC组TGF-β1、胶原-1和α-SMA的表达明显低于TAA组（P <0.01）。我们还证实了TGF-β1信号通路的下游效应子P-Smad 3/Smad 3，并发现MSC移植抑制Smad 3磷酸化。BM-MSC治疗减轻了TAA诱导的肝硬化大鼠的肝纤维化，提高了BM-MSC在肝硬化治疗中的临床应用的可能性。本文的在线版本（doi：10.1186/s12876-014-0198-6）包含补充材料，可供授权用户使用。
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. 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. 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. 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. The online version of this article (doi:10.1186/s12876-014-0198-6) contains supplementary material, which is available to authorized users.
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DOI：
10.1111/j.1440-1746.2011.07006.x
发表时间：
2012-03-01
影响因子：
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10.1073/pnas.0409722102
发表时间：
2005-03-01
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