Substrate coated with autologous decellularized extracellular matrix facilitates in vitro spreading of spheroid from adipose-derived stem cells through regulating ERK1/2-MMP2/9 pathway.

ABSTRACT

Adipose-derived stem cells (ADSCs) are easily available and play an important role in regenerative medicine. In recent years, Cell spheroid models have been in the spotlight because of their various advantages and physiological proximity. Promoting the spreading of ADSCs spheroids may improve the therapeutic effect the transplanted ADSCs. In this study, we prepared autologous decellularized extracellular matrix (d-ECM) and ADSCs spheroids, and investigated in vitro spreading of the spheroids on the d-ECM-coated substrate. In addition, the effect of d-ECM powder (ECM-P) on the aggregation of ADSCs was analyzed in a three-dimensional (3D) culture system. The results showed that d-ECM accelerated the spreading of spheroids, and promoted the migration and proliferation of the surrounding monolayer cells, accompanied by ERK1/2 activation and an increase in the expression of MMP2 and MMP9. In addition, ECM-P facilitated the aggregation of free cells in 3D culture in a concentration-dependent way. The spheroid spreading and cell aggregation were both prevented by ERK1/2 selective inhibitor PD98059. Our data suggest that the d-ECM substrate and its derivant may regulate the transformation between ADSCs spheroids and the monolayer or free cells, and ERK1/2 signalling pathway may be involved in these processes.