Lung epithelial cells induce endodermal differentiation in mouse mesenchymal bone marrow stem cells by paracrine mechanism
Lung epithelial cells induce endodermal differentiation in mouse mesenchymal bone marrow stem cells by paracrine mechanism
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DOI：
10.1089/ten.2007.0001
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发表时间：
2007-10-01
影响因子：
--
通讯作者：
Matthay, Michael A.
中科院分区：
文献类型：
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作者：
Popov, Boris V.;Serikov, Vladimir B.;Matthay, Michael A.
骨髓间充质干细胞（MSCs）是重建治疗的潜在来源。在体外，间充质干细胞分化为中胚层和外胚层细胞，但很少分化为内胚层细胞。我们建立了一个体外模型，通过MSCs和转化的肺上皮细胞（A-549）共培养来研究MSCs的内胚层分化。使用细胞不透膜分离细胞，以消除细胞融合的可能性。在这些条件下，MSCs表达了几种肺上皮标记物（细胞角蛋白5、8、14、18、19、前表面活性剂蛋白C、闭塞带-1），通过定量逆转录酶聚合酶链反应和Western blot检测，β -连环蛋白信号在MSCs中被激活。用10 - 20mM氯化锂处理MSCs激活了β -catenin通路并增强了上皮标志物的表达，尽管这种激活是短暂的。我们得出结论，a- 549细胞可以通过旁分泌机制触发MSCs的上皮分化，该机制可能包括激活β -连环蛋白信号。
Mesenchymal stem cells (MSCs) from bone marrow are a potential source for reconstructive therapy. In vitro, MSCs differentiate into cells of mesodermal and ectodermal lineages but rarely into cells of endodermal lineage. We developed an in vitro model to study the endodermal differentiation of MSCs using co-culture of MSCs and transformed lung epithelial (A-549) cells. The cells were separated using a cell-impermeable membrane to eliminate the possibility of cell fusion. Under these conditions, MSCs expressed several lung epithelial markers (cytokeratins 5, 8, 14, 18, 19, pro-surfactant protein C, zonula occludens-1), detected using quantitative reverse transcriptase polymerase chain reaction and Western blot, and beta-catenin signaling was activated in MSCs. Treatment of MSCs with 10 to 20mM lithium chloride activated the beta-catenin pathway and enhanced expression of epithelial markers, although this activation was transient. We conclude that A-549 cells can trigger epithelial differentiation of MSCs by a paracrine mechanism that may include activation of beta-catenin signaling.