Dynamic matrix potentiates mesenchymal stromal cells paracrine function via effective mechanical dose

Paracrine function of mesenchymal stromal cells (MSCs) contributes a lot to tissue development, which is regulated by several physical factors. Moreover, extracellular matrix (ECM) of MSCs is dynamic and its remdoeling always exists. Especially the change of stiffness is common. Accordingly, the ECM stiffness change may affect paracrine function of MSCs, which has less been investigated. In this study, for the first time, alginate hydrogels with different stiffening time were used to assess the influence of dynamic change of ECM stiffness paracrine functions of MSCs. It was found that the stiffer matrix (14.72 ± 1.44 kPa) under a static condition without any additional treatments could significantly potentiate the paracrine functions of MSCs paracrine compared to that of soft matrix (2.44 ± 0.23 kPa). Furthermore, this promotion was depended on the activation of Yes-associated protein (YAP) which caused by the polymerization of F-action. Intriguingly, in a dynamic system, the MSCs encapsulated-matrix which stiffened at the third day had a stronger YAP activation than that of static-stiff matrix. However, this activation was weakened when MSCs cultured in matrix which stiffened at the fifth day. The results presented that the increase of the mechanical dose of ECM would promote the paracrine functions of MSCs. Moreover, an effective mechanical dose which influence paracrine functions of MSCs indeed exists.