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

Author(s): Sharada Paudel, Lumanti Manandhar, Tyler Feltham, Lew Schon, Zijun Zhang

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.