The sources of parenchymal regeneration after chronic hepatocellular liver injury in mice
The sources of parenchymal regeneration after chronic hepatocellular liver injury in mice
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DOI：
10.1002/hep.21018
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发表时间：
2006-02-01
期刊：
影响因子：
13.5
通讯作者：
Forbes, SJ
中科院分区：
文献类型：
--
作者：
Vig, P;Russo, FP;Forbes, SJ
肝损伤后，实质再生通过肝细胞复制发生。然而，在再生应激过程中，卵圆细胞（OC）和小肝细胞样祖细胞（SHPC）有助于这一过程。本文系统地研究了B型肝炎表面抗原（HBsAg）-tg小鼠慢性肝损伤模型中肝细胞替代的肝内和肝外来源。雌鼠接受了来自雄鼠的骨髓移植，这些动物中有一半接受了逆转录酶抑制剂来阻断肝细胞的增殖。在BM移植后3个月和6个月检查肝脏以获得BM源性肝细胞、OC和SHPC的证据。在没有接受倒甲草碱的动物中，实质再生通过肝细胞复制发生，并且BM很少有助于肝细胞再生。在接受反曲马新的小鼠中，在3个月时4.8%的肝细胞为Y染色体阳性，但这通常归因于固有肝细胞和供体BM之间的细胞融合，并且在6个月时其频率降低至1.6%，因为出现了华丽的OC反应和SHPC结节。通过连续切片分析和三维图像重建，可以看到连续流的OC包围并深入SHPC的结节，与SHPC直接连接，这表明OC向SHPC转化。总之，在再生应激过程中，骨髓对实质再生的贡献很小，通常归因于细胞融合。OC和SHPC均为肝内起源，OC可形成SHPC结节。
After liver injury, parenchymal regeneration occurs through hepatocyte replication. However, during regenerative stress, oval cells (OCs) and small hepatocyte like progenitor cells (SHPCs) contribute to the process. We systematically studied the intra-hepatic and extrahepatic sources of liver cell replacement in the hepatitis B surface antigen (HBsAg-tg) mouse model of chronic liver injury. Female HBsAg-tg mice received a bone marrow (BM) transplant from male HBsAg-negative mice, and half of these animals received retrorsine to block indigenous hepatocyte proliferation. Livers were examined 3 and 6 months post-BM transplantation for evidence of BM-derived hepatocytes, OCs, and SHPCs. In animals that did not receive retrorsine, parenchymal regeneration occurred through hepatocyte replication, and the BM very rarely contributed to hepatocyte regeneration. In mice receiving retrorsine, 4.8% of hepatocytes were Y chromosome positive at 3 months, but this was frequently attributable to cell fusion between indigenous hepatocytes and donor BM, and their frequency decreased to 1.6% by 6 months, as florid OC reactions and nodules of SHPCs developed. By analyzing serial sections and reconstructing a 3-dimensional map, continuous streams of OCs could be seen that surrounded and entered deep into the nodules of SHPCs, connecting directly with SHPCs, suggesting a conversion of OCs into SHPCs. In conclusion, during regenerative stress, the contribution to parenchymal regeneration from the BM is minor and frequently attributable to cell fusion. OCs and SHPCs are of intrinsic hepatic origin, and OCs can form SHPC nodules.