Lung Epithelial Cells Induce Endodermal Differentiation in Mouse Mesenchymal Bone Marrow Stem Cells by Paracrine Mechanism (original) (raw)

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 cellimpermeable 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 b-catenin signaling was activated in MSCs. Treatment of MSCs with 10 to 20 mM lithium chloride activated the b-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 b-catenin signaling.