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首页> 外文期刊>Stem Cell Research & Therapy >Human liver mesenchymal stem/progenitor cells inhibit hepatic stellate cell activation: in vitro and in vivo evaluation
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Human liver mesenchymal stem/progenitor cells inhibit hepatic stellate cell activation: in vitro and in vivo evaluation

机译：人肝间充质干/祖细胞抑制肝星状细胞的活化：体外和体内评价

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Background Progressive liver fibrosis leads to cirrhosis and end-stage liver disease. This disease is a consequence of strong interactions between matrix-producing hepatic stellate cells (HSCs) and resident and infiltrating immune cell populations. Accumulated experimental evidence supports the involvement of adult-derived human liver mesenchymal stem/progenitor cells (ADHLSCs) in liver regeneration. The aim of the present study was to evaluate the influence of ADHLSCs on HSCs, both in vitro and in vivo. Methods Activated human HSCs were co-cultured with ADHLSCs or ADHLSC-conditioned culture medium. The characteristics of the activated human HSCs were assessed by microscopy and biochemical assays, whereas proliferation was analyzed using flow cytometry and immunocytochemistry. The secretion profile of activated HSCs was evaluated by ELISA and Luminex. ADHLSCs were transplanted into a juvenile rat model of fibrosis established after co-administration of phenobarbital and CCl4. Results When co-cultured with ADHLSCs or conditioned medium, the proliferation of HSCs was inhibited, beginning at 24?h and for up to 7?days. The HSCs were blocked in G0/G1 phase, and showed decreased Ki-67 positivity. Pro-collagen I production was reduced, while secretion of HGF, IL-6, MMP1, and MMP2 was enhanced. Neutralization of HGF partially blocked the inhibitory effect of ADHLSCs on the proliferation and secretion profile of HSCs. Repeated intrahepatic transplantation of cryopreserved/thawed ADHLSCs without immunosuppression inhibited the expression of markers of liver fibrosis in 6 out of 11 rats, as compared to their expression in the vehicle-transplanted group. Conclusions These data provide evidence for a direct inhibitory effect of ADHLSCs on activated HSCs, which supports their development for the treatment of liver fibrosis.
机译：背景技术进行性肝纤维化会导致肝硬化和终末期肝病。该疾病是产生基质的肝星状细胞（HSC）与驻留和浸润免疫细胞群体之间强烈相互作用的结果。积累的实验证据支持成人来源的人肝间充质干/祖细胞（ADHLSCs）参与肝再生。本研究的目的是评估ADHLSC对HSC的体外和体内影响。方法将活化的人HSC与ADHLSC或ADHLSC条件培养基共培养。通过显微镜和生化分析评估活化的人HSC的特征，而使用流式细胞仪和免疫细胞化学分析增殖。通过ELISA和Luminex评估活化的HSC的分泌概况。将ADHLSCs移植入苯巴比妥和CCl 4 共同给药后建立的幼年大鼠纤维化模型。结果与ADHLSCs或条件培养基共培养时，HSCs的增殖受到抑制，从24小时开始，长达7天。 HSCs在G0 / G1期受阻，并显示Ki-67阳性率降低。胶原蛋白I的产生减少，而HGF，IL-6，MMP1和MMP2的分泌增加。 HGF的中和部分地阻断了ADHLSC对HSC的增殖和分泌特征的抑制作用。与在载体移植组中的表达相比，在没有免疫抑制的情况下重复冷冻保存/解冻的ADHLSCs的肝内移植抑制了11只大鼠中6只肝纤维化标志物的表达。结论这些数据为ADHLSCs对活化的HSCs的直接抑制作用提供了证据，这支持了它们在肝纤维化治疗中的发展。

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