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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Little evidence of bone marrow-derived hepatocytes in the replacement of injured liver
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Little evidence of bone marrow-derived hepatocytes in the replacement of injured liver

机译：骨髓损伤性肝细胞置换的证据很少

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摘要

We have tested the ability of bone marrow (BM) cells (BMCs) to form hepatocytes in liver injury models. We used three models: (ⅰ) carbon tetrachloride (CCl_4) treatment, (ⅱ) albumin-urokinase transgenic mouse [TgN(Alb1Plau)], and (ⅲ) hepatitis B transgenic mouse [TgN(Alb1HBV)]. As a nonselective liver injury model, irradiated C57BL/6 (B6) mice were transplanted with BMCs from GFP transgenic mouse [TgN(ActbEGFP)] or β-galactosidase transgenic mouse [TgN(MtnLacZ)] followed by the administration of CCI_4. Irradiated TgN(Alb1HBV) and TgN(Alb1Plau) were also transplanted with BMCs from TgN(ActbEGFP) or TgN(MtnLacZ). Approximately 1.5 x 10~6 hepatocytes per liver were analyzed for GFP-positive cells, and the whole livers were inspected for β -galactosidase expression. No GFP-positive hepatocytes and no gross blue staining of the livers with 5-bromo-4-chloro-3-indolyl β-D-galactoside in any of the 18 recipient mice analyzed were detected. The livers from female animals with gender-mismatched BM transplantation were also tested with Y chromosome fluorescent in situ hybridization analysis to detect donor-derived cells. A total of five isolated hepatocytes were positive for Y chromosome in 4.1 x 10~5 hepatocytes analyzed. Our results demonstrate that there is little or no contribution of BMCs to the replacement of injured livers in these models. We conclude that BM-derived cells cannot generally lead to a cure of liver damage.
机译：我们已经在肝损伤模型中测试了骨髓（BM）细胞（BMC）形成肝细胞的能力。我们使用了三种模型：（ⅰ）四氯化碳（CCl_4）处理，（ⅱ）白蛋白-尿激酶转基因小鼠[TgN（Alb1Plau）]和（ⅲ）乙型肝炎转基因小鼠[TgN（Alb1HBV）]。作为非选择性肝损伤模型，将辐照过的C57BL / 6（B6）小鼠移植有GFP转基因小鼠[TgN（ActbEGFP）]或β-半乳糖苷酶转基因小鼠[TgN（MtnLacZ）]的BMC，然后给予CCI_4。还用来自TgN（ActbEGFP）或TgN（MtnLacZ）的BMC移植受辐照的TgN（Alb1HBV）和TgN（Alb1Plau）。分析每个肝脏大约1.5 x 10〜6个肝细胞的GFP阳性细胞，并检查整个肝脏的β-半乳糖苷酶表达。在所分析的18只受体小鼠中，没有检测到GFP阳性肝细胞，并且未检测到带有5-溴-4-氯-3-吲哚基β-D-半乳糖苷的肝脏的总蓝染色。还使用Y染色体荧光原位杂交分析测试了性别不匹配BM移植的雌性动物的肝脏，以检测供体来源的细胞。在分析的4.1 x 10〜5个肝细胞中，总共有5个分离的肝细胞Y染色体阳性。我们的结果表明，在这些模型中，BMC很少或根本没有对受伤的肝脏进行替换。我们得出的结论是，BM源性细胞通常不能治愈肝损伤。

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