Differentiation Stages of Mesenchymal Stromal Cells Change the Osteogenic Induction Capacity of Extracellular Vesicles They Derived

This study investigated the osteogenic induction potential by extracellular vesicles (EVs) produced by undifferentiated and osteogenically differentiated bone marrow-derived MSCs (BM-MSCs) on adipose-tissue derived MSCs (AT-MSCs). Osteogenic differentiation of BM-MSCs was induced with osteogenic differentiation medium. EVs were isolated from osteogenically differentiated and undifferentiated BM-MSCs (designated as Ev-os and Ev, respectively). AT-MSCs were cultured with: 1) regular medium; 2) osteogenic differentiation medium; 3) osteogenic differentiation medium with Ev; 4) osteogenic differentiation medium with Ev-os. After three weeks of culture, AT-MSCs in regular medium showed no sign of osteogenic differentiation. There were sporadic spots of mineral deposition in the AT-MSCs cultured in osteogenic differentiation medium and osteogenic medium plus Ev. Culturing in osteogenic differentiation medium plus Ev-os, AT-MSCs increased matrix mineralization more than two-fold compared with those cultured in osteogenic medium plus Ev. In conclusion, EVs produced by osteogenically differentiated MSCs are more potent in inducing osteogenic differentiation of MSCs.