Emerging Strategies for Stem Cell Lineage Commitment in Tissue Engineering and Regenerative Medicine

Stem cells have transformed the fields of tissue engineering and regenerative medicine, and their potential to further advance these fields cannot be overstated. The stem cell niche is a dynamic microenvironment that determines cell fate during development and tissue repair following an injury. Classically, stem cells were studied in isolation of their microenvironment; however, contemporary research has produced a myriad of evidence that shows the importance of multiple aspects of the stem cell niche in regulating their processes. In the context of tissue engineering and regenerative medicine studies, the niche is an artificial environment provided by culture conditions. In vitro culture conditions may involve coculturing with other cell types, developing specific biomaterials, and applying relevant forces to promote the desired lineage commitment. Considerable advance has been made over the past few years toward directed stem cell differentiation; however, the unspecific differentiation of stem cells yielding a mixed population of cells has been a challenge. In this review, we provide a systematic review of the emerging strategies used for lineage commitment within the context of tissue engineering and regenerative medicine. These strategies include scaffold pore-size and pore-shape gradients, stress relaxation, sonic and electromagnetic effects, and magnetic forces. Finally, we provide insights and perspectives into future directions focusing on signaling pathways activated during lineage commitment using external stimuli.