Abstract
Mesenchymal stem/stromal cells (MSCs) obtained from pluripotent stem cells (PSCs) constitute an interesting alternative to classical MSCs in regenerative medicine. Among their many mechanisms of action, MSC extracellular vesicles (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 is lacking. In this work, we used a label-free liquid chromatography tandem mass spectrometry proteomic approach to identify the most abundant proteins in EVs that are secreted from MSCs derived from PSCs (PD-MSCs) and from their parental induced PSCs (iPSCs). Next, we compared both datasets and found that while iPSC EVs enclose proteins that modulate RNA and microRNA stability and protein sorting, PD-MSC EVs are rich in proteins that organize extracellular matrix, regulate locomotion, and influence cell–substrate adhesion. Moreover, compared to their respective cells, iPSCs and 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 and their EVs. Altogether, these findings suggest that during differentiation, compared with their parental iPSC EVs, PD-MSC EVs acquire a more specific set of proteins; arguably, this difference might confer their therapeutic properties.
Highlights
Mesenchymal stem/stromal cells (MSCs) are one of the most promising cell types in regenerative medicine
Cell culture WA09 human embryonic stem cells were purchased from WiCell (Madison, WI, USA). induced PSCs (iPSCs) were generated in our laboratory as previously described[32]
Transmission electron microscopy (TEM) of iPSCs and PD-MSC extracellular vesicles (EVs) prepared in this work revealed vesicles of approximately 107 ± 12 and 101 ± 15 nm, respectively
Summary
Mesenchymal stem/stromal cells (MSCs) are one of the most promising cell types in regenerative medicine. Because of their multilineage differentiation potential[1] and immunological modulatory properties[2,3,4,5], MSCs are currently being tested in more than 6900 clinical studies OR Mesenchymal Stromal Cells OR MSCs, searched on December 2017). MSC therapeutic properties decline rapidly in vitro with the number of passages[10,11]. This poses a Official journal of the Korean Society for Biochemistry and Molecular Biology
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