Mechanical signals as regulators of stem cell fate.

In recent years, stem cells have shown significant promise for their potential to provide a source of undifferentiated progenitor cells for therapeutic applications in tissue or organ repair. Significant questions still remain, however, as to the genetic and epigenetic signals that regulate the fate of stem cells. It is now well accepted that the micro-environment of the stem cell can have a significant influence on its differentiation and phenotypic expression. Although emphasis has been placed in previous work on the role of soluble mediators such as growth factors and cytokines on stem cell differentiation, there is now significant evidence, both direct and indirect, that mechanical signals may also regulate stem cell fate. We review a number of in vivo and in vitro studies that have provided evidence that mechanical factors have the ability to influence the differentiation of a number of cells that have been classified as either precursor, progenitor, or stem cells. Taken together, these studies show that specific mechanical signals may promote cell differentiation into a particular phenotype, potentially having an effect on embryonic development. The use of such mechanical signals in vitro in specially designed "bioreactors" may provide important adjuncts to standard biochemical signaling pathways for promoting engineered tissue growth. A further understanding of the biomechanical and biochemical pathways involved in mechanical signal transduction by stem cells will hopefully provide new insight for the improvement of stem-cell based therapies.