Extracellular Matrix Tunes the Regenerative Potential of Fetal Stem Cells

Adult mesenchymal stem cells (MSCs) are a promising cell source for tissue regeneration. However, ex vivo expansion results in cell senescence; cells lose their proliferation and differentiation capacity. Fetal MSCs can offer an alternative due to their robust proliferation and differentiation capacities, as well as their immune privilege properties. Given the rejuvenation effect of the decellularized extracellular matrix (dECM) on adult MSCs, it remains unknown whether dECM influences the regenerative potential of fetal stem cells. In this study, passage five fetal nucleus pulposus cells (fNPCs) and fetal synovium-derived stem cells (fSDSCs) were expanded on dECMs deposited by fNPCs (NECM) and fSDSCs (SECM) for one passage, with expansion on tissue culture plastic (Plastic) as a control. We found that dECM-expanded fNPCs and fSDSCs exhibited both similarities and differences in the expression of stemness genes and surface markers. Expanded fNPCs yielded more differentiated pellets after chondrogenic induction but exhibited no adipogenic differentiation following adipogenic induction in both the Plastic and dECM groups than the corresponding fSDSC group. Despite a significant increase in fNPCs, the dECM-expanded fSDSCs exhibited no increase in chondrogenic potential; however, compared to the Plastic group, dECM-expanded fSDSCs exhibited a small increase in osteogenic potential and a great increase in adipogenic potential. These results suggest that fNPCs are more sensitive to NECM rejuvenation for cartilage tissue engineering and regeneration; in contrast, the dECMs exhibited limited effects on fSDSC rejuvenation in a chondrogenic capacity, except for enhanced adipogenic capacity following expansion on SECM.