Role of biomechanical forces in stem cell vascular lineage differentiation

Mechanical forces have long been known to play a role in the maintenance of vascular homeostasis in the mature animal and in developmental regulation in the fetus. More recently, it has been shown that stem cells play a role in vascular repair and remodeling in response to biomechanical stress. Laminar shear stress can directly activate growth factor receptors on stem/progenitor cells, initiating signaling pathways leading toward endothelial cell differentiation. Cyclic strain can stimulate stem cell differentiation toward smooth muscle lineages through different mechanisms. In vivo, blood flow in the coronary artery is significantly altered after stenting, leading to changes in biomechanical forces on the vessel wall. This disruption may activate stem cell differentiation into a variety of cells and cause delayed re-endothelialization. Based on progress in the research field, the present review aims to explore the role of mechanical forces in stem cell differentiation both in vivo and in vitro and to examine what this means for the application of stem cells in the clinic, in tissue engineering, and for the management of aberrant stem cell contribution to disease.