Proliferation and differentiation of fetal liver epithelial progenitor cells after transplantation into adult rat liver
Proliferation and differentiation of fetal liver epithelial progenitor cells after transplantation into adult rat liver
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DOI：
10.1016/s0002-9440(10)65074-2
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发表时间：
2000-06-01
影响因子：
6
通讯作者：
Shafritz, DA
中科院分区：
文献类型：
--
作者：
Dabeva, MD;Petkov, PM;Shafritz, DA
为了鉴定具有增殖和分化为肝小叶所有上皮成分的能力的细胞，我们从 ED 14 Fischer (F) 344 大鼠中分离胎儿肝上皮细胞 (FLEC)，并将这些细胞与三分之二部分肝切除术一起移植到正常和经逆转录酶 (Rs) 处理的同源二肽基肽酶 IV 的肝脏中 突变（DPPIV-）F344大鼠，使用双标记免疫组织化学/原位杂交，鉴定了FLEC的三个亚群：表达甲胎蛋白（AFP）和白蛋白的细胞，但不表达CK-19；表达CK-19但不表达AFP或白蛋白的细胞，以及表达AFP、白蛋白和细胞角蛋白-19 (CK-19)的细胞，两种模型中移植的FLEC的增殖、分化和扩增存在显着差异。在正常肝脏中，移植后1至2周，主要是具有单一表型的细胞、肝细胞（表达AFP和白蛋白）或胆管细胞（仅表达CK-19）增殖。在经Rs处理的大鼠中，内源性肝细胞的增殖能力受损，移植细胞主要表现出双重表型（同时表达AFP/白蛋白和CK-19），移植后1个月，植入实质的DPPIV+FLEC表现出肝细胞表型并产生新的肝索结构。 FLEC位于胆管附近，表现出胆管上皮表型并形成新的胆管结构或并入预先存在的胆管中。在没有增殖刺激的情况下，ED 14 FLEC 不会增殖或分化。我们的结果表明，14 天胎儿肝脏含有谱系定型（单能）和非定型（双能）祖细胞，发挥不同的再增殖能力，这些细胞受到受体肝脏的增殖状态和移植细胞植入的肝脏内宿主位点的影响。这些发现对未来针对肝脏重建和离体基因治疗的研究具有重要意义。
To identify cells that have the ability to proliferate and differentiate into all epithelial components of the liver lobule, we isolated fetal Liver epithelial cells (FLEC) from ED 14 Fischer (F) 344 rats and transplanted these cells in conjunction with two-thirds partial hepatectomy into the liver of normal and retrorsine (Rs) treated syngeneic dipeptidyl peptidase IV mutant (DPPIV-) F344 rats, Using dual label immunohistochemistry/in situ hybridization, three subpopulations of FLEC were identified: cells expressing both alpha-fetoprotein (AFP) and albumin, but not CK-19; cells expressing CK-19, but not AFP or albumin, and cells expressing AFP, albumin, and cytokeratins-19 (CK-19), Proliferation, differentiation, and expansion of transplanted FLEC differed significantly in the two models. In normal liver, 1 to 2 weeks after transplantation, mainly cells with a single phenotype, hepatocytic (expressing AFP and albumin) or bile ductular (expressing only CK-19), had proliferated. In Rs-treated rats, in which the proliferative capacity of endogenous hepatocytes is impaired, transplanted cells showed mainly a dual phenotype (expressing both AFP/albumin and CK-19), One month after transplantation, DPPIV+ FLEC engrafted into the parenchyma exhibited an hepatocytic phenotype and generated new hepatic cord structures. FLEC, localized in the vicinity of bile ducts, exhibited a biliary epithelial phenotype and formed new bile duct structures or were incorporated into pre-existing bile ducts. In the absence of a proliferative stimulus, ED 14 FLEC did not proliferate or differentiate. Our results demonstrate that 14-day fetal liver contains lineage committed (unipotential) and uncommitted (bipotential) progenitor cells exerting different repopulating capacities, which are affected by the proliferative status of the recipient liver and the host site within the liver where the transplanted cells become engrafted. These findings have important implications in future studies directed toward liver repopulation and ex vivo gene therapy.