Extracellular vesicles from pluripotent stem cell-derived mesenchymal stem cells acquire a stromal modulatory proteomic pattern during differentiation

LA GRECA, ALEJANDRO; SOLARI, CLAUDIA; FURMENTO, VERONICA; LOMBARDI, ANTONELLA; BIANI, MARIA CELESTE; ABAN, CYNTIA; MORO, LUCIA; GARCÍA, MARCELA; GUBERMAN, ALEJANDRA SONIA; SEVLEVER, GUSTAVO EMILIO; MIRIUKA, SANTIAGO GABRIEL; LUZZANI, CARLOS

Experimental & Molecular Medicine

Nature publishing group

Año: 2018 vol. 50

Mesenchymal stem/stromal cells (MSCs) obtained from pluripotent stem cells (PSCs) constitute an interestingalternative to classical MSCs in regenerative medicine. Among their many mechanisms of action, MSC extracellularvesicles (EVs) are a potential suitable substitute for MSCs in future cell-free-based therapeutic approaches. Unlike cells,EVs do not elicit acute immune rejection, and they can be produced in large quantities and stored until ready to use.Although the therapeutic potential of MSC EVs has already been proven, a thorough characterization of MSC EVs islacking. In this work, we used a label-free liquid chromatography tandem mass spectrometry proteomic approach toidentify the most abundant proteins in EVs that are secreted from MSCs derived from PSCs (PD-MSCs) and from theirparental induced PSCs (iPSCs). Next, we compared both datasets and found that while iPSC EVs enclose proteins thatmodulate RNA and microRNA stability and protein sorting, PD-MSC EVs are rich in proteins that organize extracellularmatrix, regulate locomotion, and influence cell?substrate adhesion. Moreover, compared to their respective cells, iPSCsand iPSC EVs share a greater proportion of proteins, while the PD-MSC proteome appears to be more specific.Correlation and principal component analysis consistently aggregate iPSCs and iPSC EVs but segregate PD-MSC andtheir EVs. Altogether, these findings suggest that during differentiation, compared with their parental iPSC EVs, PDMSCEVs acquire a more specific set of proteins; arguably, this difference might confer their therapeutic properties.