Unraveling the mechanistic effects of electric field stimulation towards directing stem cell fate and function: A tissue engineering perspective.

Electric field (EF) stimulation can play a vital role in eliciting appropriate stem cell response. Such an approach is recently being established to guide stem cell differentiation through osteogenesis/neurogenesis/cardiomyogenesis. Despite significant recent efforts, the biophysical mechanisms by which stem cells sense, interpret and transform electrical cues into biochemical and biological signals still remain unclear. The present review critically analyses the variety of EF stimulation approaches that can be employed to evoke appropriate stem cell response and also makes an attempt to summarize the underlying concepts of this notion, placing special emphasis on stem cell based tissue engineering and regenerative medicine. This review also discusses the major signaling pathways and cellular responses that are elicited by electric stimulation, including the participation of reactive oxygen species and heat shock proteins, modulation of intracellular calcium ion concentration, ATP production and numerous other events involving the clustering or reassembling of cell surface receptors, cytoskeletal remodeling and so on. The specific advantages of using external electric stimulation in different modalities to regulate stem cell fate processes are highlighted with explicit examples, in vitro and in vivo.