Application of External Force Regulates the Migration and Differentiation of Adipose-Derived Stem/Progenitor Cells by Altering Tissue Stiffness.

Large soft-tissue defects are challenging to reconstruct surgically. Expansion of soft tissue using an external volume expansion (EVE) device is a noninvasive method to improve such reconstruction; however, the underlying mechanism is unclear. In this study, we created fat flaps in Sprague-Dawley rats, applied an external force of 3 or 6 kPa using an EVE device, and investigated the migration and differentiation of adipose-derived stem/progenitor cells (ASCs). In addition, we performed finite element analysis to explore the stiffness of adipose tissue. An external force of 3 kPa promoted the migration and adipogenic differentiation of ASCs. By comparison, an external force of 6 kPa had a larger effect on migration of ASCs, but a smaller effect on adipogenic differentiation of ASCs. External force affected adipose tissue stiffness. In conclusion, external force generated by an EVE device increases the stiffness of adipose tissue, which influences the migration and differentiation of ASCs. The size of the external force can be altered according to the tissue stiffness required at particular time points to promote long-term adipose tissue regeneration. Impact Statement Stem cell therapy in clinic mostly requires the addition of exogenous stem cells, therefore the safety and controllability is always defective. In this study, the external force of external volume expansion regulates adipose-derived stem/progenitor cells (ASCs) migration and differentiation through tissue stiffness. Using tissue engineering without exogenous ASCs can promote long-term adipose tissue regeneration. The findings of this study provide theoretical support for clinical tissue engineering applications and improvements in stem cell therapy.