Shear Stress Induces Endothelial Differentiation From a Murine Embryonic Mesenchymal Progenitor Cell Line

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Abstract
Objective— Recent studies have illustrated that mesenchymal stem cells possess the potential to differentiate along an endothelial lineage, but the effect of shear on mesenchymal differentiation is unknown. Thus, we developed an in vitro shear stress system to examine the relationship between shear stress and the endothelial differentiation of a murine embryonic mesenchymal progenitor cell line, C3H/10T1/2. Methods and Results— The parallel plate system of fluid shear stress was used. Shear stress significantly induced expression of mature endothelial cell–specific markers in CH3H/10T1/2 cells such as CD31, von Willebrand factor, and vascular endothelial–cadherin at both the mRNA and protein levels with real-time polymerase chain reaction and immunofluorescence analyses, respectively. In addition, shear-induced augmentation of functional markers of the mature endothelial phenotype such as uptake of acetylated low-density lipoproteins and formation of capillary-like structures on Matrigel. Furthermore, shear stress significantly upregulated angiogenic growth factors while downregulating growth factors associated with smooth muscle cell differentiation. Conclusions— This study demonstrates, for the fist time, endothelial differentiation in a mesenchymal progenitor CH3H/10T1/2 cell line resulting from shear exposure. Thus, this analysis may serve as a basis for further understanding the effect of shear on mesenchymal and vascular cell differentiation.