The Therapeutic Potential of Human Umbilical Mesenchymal Stem Cells from Wharton's Jelly in the Treatment of Rat Liver Fibrosis
The Therapeutic Potential of Human Umbilical Mesenchymal Stem Cells from Wharton's Jelly in the Treatment of Rat Liver Fibrosis
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DOI：
10.1002/lt.21715
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发表时间：
2009-05-01
影响因子：
4.6
通讯作者：
Fu, Yu-Show
中科院分区：
文献类型：
--
作者：
Tsai, Pei-Chun;Fu, Tz-Win;Fu, Yu-Show
我们研究了从华顿氏胶中提取的人脐带间充质干细胞（HUMSC）对四氯化碳（CCl 4）诱导的大鼠肝纤维化的影响。用CCl 4处理大鼠4周，然后将HUMSC直接注射到它们的肝脏中。经过4周以上的CCl 4处理（共8周）后，与接受CCl 4处理8周但未接受HUMSC移植的大鼠[CCl 4（8 W）]相比，接受HUMSC移植的大鼠[CCl 4（8 W）+HUMSC肝脏]表现出肝纤维化显著减少，如天狼星红染色和胶原蛋白含量测定所证明。此外，与CCl 4（8 W）组相比，CCl 4（8 W）+HUMSC（肝脏）组大鼠的血清谷草转氨酶、谷丙转氨酶、α-平滑肌肌动蛋白和肝脏转化生长因子-β 1水平显著降低，而肝脏间充质上皮转化因子-磷酸化型（Met-P）和肝细胞生长因子的表达上调。值得注意的是，移植的HUMSC主要分散在肝结缔组织中，但不分化为表达人白蛋白或甲胎蛋白的肝细胞。相反，这些移植的未分化的HUMSC分泌多种生物活性细胞因子，可以恢复肝功能并促进再生。人细胞因子测定显示，CCl 4（8 W）+HUMSC（肝脏）组肝脏中人皮肤T细胞吸引趋化因子、白血病抑制因子和催乳素的量显著更高，微正电子发射断层扫描显示肝脏炎症显著减少。我们的研究结果表明，异种移植HUMSC是一种治疗肝纤维化的新方法，可能是一个有前途的治疗干预的未来。肝移植15：484-495，2009。(C)2009年AASLD。
We investigated the effect of human umbilical mesenchymal stem cells (HUMSCs) from Wharton's jelly on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Rats were treated with CCl4 for 4 weeks, and this was followed by a direct injection of HUMSCs into their livers. After 4 more weeks of CCl4 treatment (8 weeks in all), rats with HUMSC transplants [CCl4 (8W)+HUMSC liver] exhibited a significant reduction in liver fibrosis, as evidenced by Sirius red staining and a collagen content assay, in comparison with rats treated with CCl4 for 8 weeks without HUMSC transplants [CCl4 (8W)]. Moreover, rats in the CCl4 (8W)+HUMSC (liver) group had significantly lower levels of serum glutamic oxaloacetic transaminase, glutamic pyruvate transaminase, alpha-smooth muscle actin, and transforming growth factor-beta 1 in the liver, whereas the expression of hepatic mesenchymal epithelial transition factor-phosphorylated type (Met-P) and hepatocyte growth factor was up-regulated, in comparison with the CCl4, (8W) group. Notably, engrafted HUMSCs scattered mostly in the hepatic connective tissue but did not differentiate into hepatocytes expressing human albumin or alpha-fetoprotein. Instead, these engrafted, undifferentiated HUMSCs secreted a variety of bioactive cytokines that may restore liver function and promote regeneration. Human cytokine assay revealed that the amounts of human cutaneous T cell-attracting chemokine, leukemia inhibitory factor, and prolactin were substantially greater in the livers of the CCl4 (8W)+HUMSC (liver) group, with considerably reduced hepatic inflammation manifested by a micro positron emission tomography scan. Our findings suggest that xenogeneic transplantation of HUMSCs is a novel approach for treating liver fibrosis and may be a promising therapeutic intervention in the future. Liver Transpl 15: 484-495, 2009. (C) 2009 AASLD.