Isolation of a bone marrow-derived stem cell line with high proliferation potential and its application for preventing acute fatal liver failure
Isolation of a bone marrow-derived stem cell line with high proliferation potential and its application for preventing acute fatal liver failure
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DOI：
10.1634/stemcells.2007-0078
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发表时间：
2007-11-01
期刊：
影响因子：
5.2
通讯作者：
Huh, Nam-Ho
中科院分区：
文献类型：
--
作者：
Miyazaki, Masahiro;Hardjo, Marhaen;Huh, Nam-Ho
肝外来源的肝细胞或肝细胞样细胞移植是治疗急性和慢性肝衰竭的一种很有前途的策略。我们研究了骨髓细胞诱导的肝细胞样细胞的可能用途。从两个不同大鼠品系的骨髓中建立了克隆细胞系。其中一种细胞系rBM25/S3细胞生长迅速（倍增时间，类似于24小时），在300天内至少300倍的群体倍增水平下，细胞特性没有任何明显变化，保持正常的二倍体核型。这些细胞表达CD29、CD44、CD49b、CD90、vimentin和纤维连接蛋白，但不表达CD45，表明它们是间充质细胞来源。将肝细胞生长因子和成纤维细胞生长因子-4在Matrigel上处理后，细胞有效分化为表达白蛋白、细胞色素P450 (CYP) 1A1、CYP1A2、葡萄糖6-磷酸酶、色氨酸-2,3-双加氧酶、酪氨酸转氨酶、肝细胞核因子（HNF）1 α和HNF4 α的肝细胞样细胞。分化细胞脾内移植可预防90%肝切除大鼠致死性肝衰竭。综上所述，从成年大鼠骨髓中提取的克隆干细胞可以分化为肝细胞样细胞，移植分化后的细胞可预防90%肝切除大鼠致死性肝衰竭。目前的结果显示了治疗人类致命性肝病的一个有希望的策略。
Transplantation of hepatocytes or hepatocyte-like cells of extrahepatic origin is a promising strategy for treatment of acute and chronic liver failure. We examined possible utility of hepatocyte-like cells induced from bone marrow cells for such a purpose. Clonal cell lines were established from the bone marrow of two different rat strains. One of these cell lines, rBM25/S3 cells, grew rapidly (doubling time, similar to 24 hours) without any appreciable changes in cell properties for at least 300 population doubling levels over a period of 300 days, keeping normal diploid karyotype. The cells expressed CD29, CD44, CD49b, CD90, vimentin, and fibronectin but not CD45, indicating that they are of mesenchymal cell origin. When plated on Matrigel with hepatocyte growth factor and fibroblast growth factor-4, the cells efficiently differentiated into hepatocyte-like cells that expressed albumin, cytochrome P450 (CYP) 1A1, CYP1A2, glucose 6-phosphatase, tryptophane-2,3-dioxygenase, tyrosine aminotransferase, hepatocyte nuclear factor (HNF)1 alpha, and HNF4 alpha. Intrasplenic transplantation of the differentiated cells prevented fatal liver failure in 90%-hepatectomized rats. In conclusion, a clonal stem cell line derived from adult rat bone marrow could differentiate into hepatocyte-like cells, and transplantation of the differentiated cells could prevent fatal liver failure in 90%-hepatectomized rats. The present results indicate a promising strategy for treating human fatal liver diseases.