Maeda Hiromichi, Ota Yoshihiro, Wang Yongchung, Ramachandran Kalyani, Montgomery Robert A, Williams George Melville, Sun Zhaoli
Department of Surgery, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research 771, Baltimore, MD 21205 USA ; Department of Surgery and Cancer Treatment Center, Kochi Medical School, Kohasu Oko-cho, Nankoku-city, Kochi, 783-8505 Japan.
Springerplus. 2013 Sep 8;2:446. doi: 10.1186/2193-1801-2-446. eCollection 2013.
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 um(2) vs. 451.3 um(2), 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.
倒千里光碱选择性抑制肝细胞增殖，在肝损伤后可诱导小肝细胞样祖细胞产生。本研究旨在探究内源性肝外细胞在倒千里光碱处理后是否对小肝细胞样祖细胞有贡献。
将经倒千里光碱处理的野生型Lewis大鼠肝脏移植到绿色荧光蛋白（GFP）转基因Lewis大鼠体内。预期GFP阳性、产生白蛋白的多边形细胞为受体来源的肝细胞样细胞。
移植50%体积的经倒千里光碱预处理的肝脏4周后，GFP阳性肝细胞样细胞的比例为0.02365%。这些细胞大多以单个细胞存在，其细胞大小显著大于正常肝细胞（平均细胞大小；799.4μm²对451.3μm²，p<0.0001）。8周时，出现了GFP阳性的小尺寸产生白蛋白的细胞簇，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染色阴性，一些细胞簇中含有较大的细胞，表明其进一步成熟。
内源性肝外细胞可在移植的经倒千里光碱预处理的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。
