From mechanical stimulation to biological pathways in the regulation of stem cell fate

Abstract

Mechanical stimuli are important in directing the fate of stem cells; the effects of mechanical stimuli reported in recent research are reviewed here. Stem cells normally undergo two fundamental processes: proliferation, in which their numbers multiply, and differentiation, in which they transform into the specialized cells needed by the adult organism. Mechanical stimuli are well known to affect both processes of proliferation and differentiation, although the complete pathways relating specific mechanical stimuli to stem cell fate remain to be elucidated. We identified two broad classes of research findings and organized them according to the type of mechanical stress (compressive, tensile or shear) of the stimulus. Firstly, mechanical stress of any type activates stretch-activated channels (SACs) on the cell membrane. Activation of SACs leads to cytoskeletal remodelling and to the expression of genes that regulate the basic growth, survival or apoptosis of the cells and thus regulates proliferation. Secondly, mechanical stress on cells that are physically attached to an extracellular matrix (ECM) initiates remodelling of cell membrane structures called integrins. This second process is highly dependent on the type of mechanical stress applied and result into various biological responses. A further process, the Wnt pathway, is also implicated: crosstalk between the integrin and Wnt pathways regulates the switch from proliferation to differentiation and finally regulates the type of differentiation. Therefore, the stem cell differentiation process involves different signalling molecules and their pathways and most likely depends upon the applied mechanical stimulation.

Keywords: crosstalk; integrin; mechanical stimulation; signalling molecules; stem cell response.