Inserm U972, University Paris-Sud, IFR 69, Hôpital du Kremlin-Bicêtre, Le Kremlin-Bicêtre, France.
Exp Cell Res. 2009 Nov 15;315(19):3396-405. doi: 10.1016/j.yexcr.2009.07.007. Epub 2009 Jul 15.
The success of hepatocyte transplantation has been limited by the low efficiency of transplanted cell integration into liver parenchyma. Human fetal hepatic progenitor cells (hepatoblasts) engraft more effectively than adult hepatocytes in mouse livers. However, the signals required for their integration are not yet fully understood. We investigated the role of HGF on the migration and invasive ability of human hepatic progenitors in vitro and in vivo. Hepatoblasts were isolated from the livers of human fetuses between 10 and 12 weeks of gestation. Their invasive ability was assessed in the presence or absence of HGF. These cells were also transplanted into immunodeficient mice and analyzed by immunohistochemistry. In contrast to TNF-alpha, HGF increased the motogenesis and invasiveness of hepatoblasts, but not of human adult hepatocytes, via phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. The invasive ability of human hepatoblasts correlated with the expression and secretion of matrix metalloproteinases (MMPs). Hepatoblasts stimulated with HGF prior transplantation into newborn mice migrated from the portal area into the hepatic parenchyma.
In contrast to adult hepatocytes, hepatoblasts display invasive ability that can be modulated by HGF in vitro and in vivo.
肝细胞移植的成功率受到转染细胞与肝实质有效整合效率低的限制。与成人肝细胞相比，人胎肝祖细胞（肝前体细胞）在小鼠肝脏中的植入效率更高。但是，其整合所需的信号仍未完全阐明。我们研究了 HGF 对人肝祖细胞体外和体内迁移和侵袭能力的作用。我们从妊娠 10 至 12 周的人胎肝中分离肝前体细胞，在存在或不存在 HGF 的情况下评估其侵袭能力。这些细胞还被移植到免疫缺陷小鼠中，并通过免疫组织化学进行分析。与 TNF-α相反，HGF 通过磷酸化细胞外信号调节激酶（ERK）1/2 增加肝前体细胞而非成人肝细胞的游走和侵袭能力。人肝前体细胞的侵袭能力与基质金属蛋白酶（MMPs）的表达和分泌相关。在移植到新生小鼠前用 HGF 刺激的肝前体细胞从门脉区迁移到肝实质中。
与成人肝细胞不同，肝前体细胞显示出可在体外和体内通过 HGF 调节的侵袭能力。
