Enhance expression of fibroblast growth factor 2 in bone marrow cells and its potential role in the differentiation of hepatic epithelial stem-like cells into the hepatocytes lineage
Enhance expression of fibroblast growth factor 2 in bone marrow cells and its potential role in the differentiation of hepatic epithelial stem-like cells into the hepatocytes lineage
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增强骨髓细胞中成纤维细胞生长因子2的表达及其在肝上皮干细胞样细胞向肝细胞谱系分化中的潜在作用
DOI：
10.1007/s00441-010-1093-2
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发表时间：
2011
期刊：
影响因子：
3.6
通讯作者：
et al
中科院分区：
文献类型：
--
作者：
Haga H;Okumoto K;Togashi H (12名中11番目);et al
骨髓细胞移植已被应用于肝脏再生细胞治疗。然而，移植的骨髓基质细胞和肝干细胞之间的相互作用的细节尚未阐明。本研究的目的是研究BMC与肝干细胞样细胞（HSLC）的相互作用，并确定BMC因子，引导HSLC分化为肝细胞系。从成年Sprague-Dawley大鼠获得BMCs和HSLCs，并建立共培养体系。通过增殖测定分析细胞增殖，并通过检测肝特异性蛋白的细胞mRNA来评估HSLC向肝细胞谱系的分化。将DNA微阵列分析应用于与HSLC共培养的BMCs，以确定通过它们的相互作用上调的基因。与BMCs共培养的HSLCs的增殖能力明显高于单独培养的HSLCs，并可检测到HSLCs中白蛋白和色氨酸-2，3-双加氧酶mRNA的表达。DNA微阵列分析显示，与HSLC共培养的BMCs中成纤维细胞生长因子2（FGF 2）mRNA表达上调，与FGF 2共培养的HSLC中可检测到白蛋白和酪氨酸氨基转移酶mRNA的表达。因此，BMC刺激HSLC的增殖及其分化成肝细胞谱系。FGF 2是由相互作用的BMCs产生并刺激这种分化的因子之一。
The transplantation of bone marrow cells (BMCs) has been applied in liver regenerative cell therapy. However, details of the interaction between the transplanted BMCs and hepatic stem cells have not been elucidated. The aim of the present study was to investigate the interaction of BMCs with hepatic stem-like cells (HSLCs) and to determine the BMC factor that steers HSLC differentiation into the hepatocyte lineage. Both BMCs and HSLCs were obtained from an adult Sprague-Dawley rat, and a co-culture system was established. Cell proliferation was analyzed by a proliferation assay, and the differentiation of HSLCs into the hepatocyte lineage was evaluated by the detection of cellular mRNA for liver-specific proteins. DNA microarray analysis was applied to BMCs co-cultured with HSLCs to determine the genes upregulated by their interaction. The proliferation of HSLCs co-cultured with BMCs was significantly higher than that of HSLCs cultured alone, and the expression of mRNAs for bothalbuminandtryptophan-2,3-dioxygenasewas detectable in the co-cultured HSLCs. DNA microarray analysis showed the upregulated expression offibroblast growth factor 2(FGF2) mRNA in BMCs co-cultured with HSLCs, and the expression of mRNAs for bothalbuminandtyrosine aminotransferasebecame detectable in HSLCs cultured with FGF2. Thus, BMCs stimulate both the proliferation of HSLCs and their differentiation into the hepatocyte lineage. FGF2 is one of the factors that is produced by the interacting BMCs and that stimulates this differentiation.