Microcarrier stiffness controls human amniotic epithelial cells (hAECs) proliferation and epithelial-mesenchymal transition (EMT) via remodeling ECM and Wnt/β-catenin pathway

Human amniotic epithelial cells (hAECs) are ideal candidates for use in regenerative medicine because of their low immunogenicities and levels of tumorigenic potential. However, the in vitro cultivation of hAECs is challenged by their limited proliferative capacities and ambiguous cellular characteristics. Microcarrier stiffness is crucial in the immediate epithelial-mesenchymal transition (EMT) of hAECs upon in vitro cultivation. By monitoring changes in cellular proliferation, phenotypic, and metabolic activity under microcarrier stiffnesses via transcriptomic analysis, this study revealed the regulatory roles of microcarrier stiffness in the proliferation and EMT progression of hAECs. An increased microcarrier stiffness inhibits the proliferation and epithelial phenotype maintenance of hAECs, which is linked to the remodeling of the extracellular matrix (ECM) and ECM-integrin interactions, in addition to the activation of the Wnt/β-catenin signaling pathway. These findings provide novel insights into the mechanical regulation of hAECs proliferation and phenotypes of hAECs, paving the way for their scale-up.