Contribution of extrahepatic small cells resembling small hepatocyte-like progenitor cells to liver mass maintenance in transplantation model of retrorsine-pretreated liver.

Contribution of extrahepatic small cells resembling small hepatocyte-like progenitor cells to liver mass maintenance in transplantation model of retrorsine-pretreated liver.
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DOI:
10.1186/2193-1801-2-446
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发表时间:
2013
期刊:
影响因子:
--
通讯作者:
Sun Z
Sun Z
中科院分区:
其他
文献类型:
--
作者:
Maeda H;Ota Y;Wang Y;Ramachandran K;Montgomery RA;Williams GM;Sun Z

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逆转录碱选择性抑制肝细胞增殖,并在肝损伤后诱发小肝细胞样祖细胞。本研究的目的是查明内源性肝外细胞在逆转录酶治疗后是否有助于形成小肝细胞样祖细胞。将暴露于逆转录酶的野生型Lewis大鼠肝脏移植到GFP转基因Lewis大鼠中。 GFP 阳性、产生白蛋白的多边形细胞预计为受体来源的肝细胞样细胞。经逆转录酶预处理的50%体积肝脏移植后4周,GFP阳性肝细胞样细胞率为0.02365%。这些细胞大多数为单细胞,其细胞大小明显大于正常肝细胞(平均细胞大小;799.4 um2 vs. 451.3 um2,p<0.0001)。第八周时,出现 GFP 阳性小尺寸白蛋白产生细胞簇,占肝细胞的 0.00759%。这些细胞的形态与小肝细胞样祖细胞相似,其中12.5%为Ki67阳性,大多数细胞CYP1A2染色呈阴性,一些细胞簇含有较大的细胞,表明进一步成熟。内源性肝外细胞可以在经逆转录酶预处理的移植肝脏中形成类似于小肝细胞样祖细胞的小细胞簇。肝外细胞对肝脏质量维持的贡献相当低,其重要性尚不清楚。本文的在线版本 (doi:10.1186/2193-1801-2-446) 包含补充材料,可供授权用户使用。
Retrorsine selectively inhibits hepatocyte proliferation and following liver injury evokes small hepatocyte-like progenitor cells. The aim of this study is to find out whether endogenous extrahepatic cells contribute to small hepatocyte-like progenitor cells after retrorsine treatment. Wild-type Lewis rat liver exposed to retrorsine was transplanted into GFP transgenic Lewis rat. GFP positive, albumin-producing polygonal cells were expected as reciepient-derived hepatocyte-like cells. Four weeks after transplantation of 50% volume of retrorsine-pretreated liver, the rate of GFP positive hepatocyte-like cells was 0.02365%. Majority of these cells resided as single cells and their cell size was significantly larger than that of normal hepatocytes (mean cell size; 799.4 um2 vs. 451.3 um2, p<0.0001). At eight weeks, clusters of GFP positive small-size albumin-producing cells appeared and occupied 0.00759% of hepatocytes. The morphology of these cells was similar to that of small hepatocyte-like progenitor cells, 12.5% of them were Ki67 positive, majority of them were negative for CYP1A2 staining, and some clusters contained larger cells indicating further maturation. Endogenous extrahepatic cells can form a cluster of small cells resembling small hepatocyte-like progenitor cells in a transplanted retrorsine-pretreated liver. The contribution of extrahepatic cells to liver mass maintenance is quite low and its importance is unclear. The online version of this article (doi:10.1186/2193-1801-2-446) contains supplementary material, which is available to authorized users.
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