The role of Piezo proteins and cellular mechanosensing in tuning the fate of transplanted stem cells

Differentiation of stem cells can be modulated by a combination of internal and external signals, including mechanical cues from the surrounding microenvironment. Although numerous chemical and biological agents have been recognized in regulating stem cells' fate, little is known about their potential to directly sense the mechanical signals to choose differentiation into a specific lineage. The success of any stem cell transplantation effort, however, hinges on thorough understanding of the fate of these cells under different signals, including mechanical cues. Various proteins are involved in the mechanical sensing process. Of these, Piezo proteins, as the ion channels activated by membrane tension and mechanical signals, play an important role in translating the information of mechanical forces such as rigidity and topography of the extracellular matrix to the intracellular signaling pathways related to stem cell homing and differentiation. They also play a key role in terms of shear stresses and tensile loads in expansion systems. This review highlights key evidence for the potential of mechanically gated ion channels expressed by human stem cells, and the mechanotransduction and past mechanomemory in the fate of transplanted stem cells. With this knowledge in mind, by controlling the tissue-specific patterns of mechanical forces in the scaffolds, we may further improve the regulation of homing, the differentiation, and the fate of transplanted stem cells.