Review Mechanobiology: A landscape for reinterpreting stem cell heterogeneity and regenerative potential in diseased tissues

Mechanical forces play a fundamental role in cellular dynamics from the molecular level to the establishment of complex heterogeneity in somatic and stem cells. Here, we highlight the role of cytoskeletal mechanics and extracellular matrix in generating mechanical forces merging into oscillatory synchronized patterns. We discuss how cellular mechanosensing/-transduction can be modulated by mechanical forces to control tissue metabolism and set the basis for nonpharmacologic tissue rescue. Control of bone anabolic activity and repair, as well as obesity prevention, through a fine-tuning of the stem cell morphodynamics are highlighted. We also discuss the use of mechanical forces in the treatment of cardiovascular diseases and heart failure through the fine modulation of stem cell metabolic activity and regenerative potential. We finally focus on the new landscape of delivering specific mechanical stimuli to reprogram tissue-resident stem cells and enhance our self-healing potential, without the need for stem cell or tissue transplantation.

Automated summary

Mechanical forces are crucial in cellular dynamics, from the molecular level to the complexity in somatic and stem cells. This article highlights the role of cytoskeletal mechanics and extracellular matrix in generating mechanical forces that lead to oscillatory synchronized patterns. It discusses how mechanical forces can modulate mechanosensing/-transduction to control tissue metabolism and enable nonpharmacologic tissue rescue. The importance of fine-tuning stem cell morphodynamics in bone anabolic activity, repair, obesity prevention, cardiovascular disease treatment, and heart failure is also emphasized. The use of specific mechanical stimuli to reprogram tissue-resident stem cells and enhance self-healing potential is explored, without the need for stem cell or tissue transplantation.