Stiffness of Hydrogels Regulates Cellular Reprogramming Efficiency Through Mesenchymal-to-Epithelial Transition and Stemness Markers

Abstract

The stiffness of hydrogels has been reported to direct cell fate. Here, we found that the stiffness of hydrogels promotes the reprogramming of mouse embryonic fibroblasts into induced pluripotent stem cells (iPSCs). We prepared cell culture substrates of various stiffnesses (0.1, 1, 4, 10, and 20 kPa) using a polyacrylamide hydrogel. We found that culture on a soft hydrogel plays an important role in inducing cellular reprogramming into iPSCs via activation of mesenchymal-to-epithelial transition and enhancement of stemness marker expression. These results suggest that physical signals at the interface between cell and substrate can be used as a potent regulator to promote cell fate changes associated with reprogramming into iPSCs, which may lead to effective and reproducible iPSC-production. The stiffness of hydrogels can be used as a potent regulator to promote cell fate changes associated with reprogramming into induced pluripotent stem cells (iPSCs) via increased mesenchymal-to-epithelial transition activity and stem cell marker expression. This study can lead to effective and reproducible iPSC production and be applied to iPSC-based therapy.