Lee J-H, Park H-J, Jang I K, Kim H-E, Lee D-H, Park J-K, Lee S-K, Yoon H-H
Samsung Biomedical Research Institute, Seoul, Republic of Korea.
Biomedical Research Institute, Lifeliver Co Ltd, Yongin, Republic of Korea.
Transplant Proc. 2014 Jun;46(5):1633-7. doi: 10.1016/j.transproceed.2013.12.070.
Liver transplantation is severely limited by donor shortage although it is the only effective treatment for end-stage liver disease. So the best alternative is hepatocyte transplantation. For obtaining human hepatocytes, some stem cells originating from extrahepatic or intraheptic tissues have been isolated and characterized. Previously we have reported that human liver-derived stem cells (HLSCs) could be isolated and expanded from donated livers unsuitable for transplantation; they expressed some markers of mesenchymal stem cells but neither hematopoietic nor oval cells. In this study, we isolated and expanded HLSCs with mesenchymal characteristics from another adult human liver. They showed mesenchymal morphology and grew well under serum condition similar to our previous reports. Also, they expressed some markers of mesenchymal stem cells, such as CD44, CD73, CD90, and CD105, through fluorescence-activated cell sorting analysis. When HLSCs were sequentially exposed to fibroblast growth factor-1 (FGF-1), FGF-4, and hepatocyte growth factor (HGF) followed by FGF-4, HGF, oncostatin M, and dexamethasone, they became round or polygonal, and expressed some hepatic markers such as albumin and α1-antitrypsin in the gene or protein level. Also, they showed urea synthesis activity 7 days after treatment of FGF-4, HGF, oncostatin M, and dexamethasone. These results provided that HLSCs would be a useful cell source in the field of regenerative medicine as well as liver cell biology.
尽管肝移植是终末期肝病的唯一有效治疗方法，但供体短缺严重限制了其应用。因此，最佳替代方案是肝细胞移植。为了获得人肝细胞，已从肝外或肝内组织中分离并鉴定了一些干细胞。此前我们报道过，人肝源性干细胞（HLSCs）可从不适于移植的捐赠肝脏中分离并扩增；它们表达一些间充质干细胞标志物，但既不表达造血细胞标志物也不表达卵圆细胞标志物。在本研究中，我们从另一例成人肝脏中分离并扩增了具有间充质特征的HLSCs。它们呈现间充质形态，并且在血清条件下生长良好，与我们之前的报道相似。此外，通过荧光激活细胞分选分析，它们表达一些间充质干细胞标志物，如CD44、CD73、CD90和CD105。当HLSCs依次暴露于成纤维细胞生长因子-1（FGF-1）、FGF-4和肝细胞生长因子（HGF），随后再暴露于FGF-4、HGF、制瘤素M和地塞米松时，它们变成圆形或多边形，并在基因或蛋白质水平表达一些肝标志物，如白蛋白和α1-抗胰蛋白酶。此外，在经FGF-4、HGF、制瘤素M和地塞米松处理7天后，它们显示出尿素合成活性。这些结果表明，HLSCs在再生医学以及肝细胞生物学领域将是一种有用的细胞来源。
