Proteomic Analysis of Microvesicles Derived from Human Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) have emerged as a promising
means
for treating degenerative or incurable diseases. Recent studies have
shown that microvesicles (MVs) from MSCs (MSC-MVs) contribute to recovery
of damaged tissues in animal disease models. Here, we profiled the
MSC-MV proteome to investigate their therapeutic effects. LC–MS/MS
analysis of MSC-MVs identified 730 MV proteins. The MSC-MV proteome
included five positive and two variable known markers of MSCs, but
no negative marker, as well as 43 surface receptors and signaling
molecules controlling self-renewal and differentiation of MSCs. Functional
enrichment analysis showed that cellular processes represented by
the MSC-MV proteins include cell proliferation, adhesion, migration,
and morphogenesis. Integration of MSC’s self-renewal and differentiation-related
genes and the proteome of MSC-conditioned media (MSC-CM) with the
MSC-MV proteome revealed potential MV protein candidates that can
be associated with the therapeutic effects of MSC-MVs: (1) surface
receptors (PDGFRB, EGFR, and PLAUR); (2) signaling molecules (RRAS/NRAS,
MAPK1, GNA13/GNG12, CDC42, and VAV2); (3) cell adhesion (FN1, EZR,
IQGAP1, CD47, integrins, and LGALS1/LGALS3); and (4) MSC-associated
antigens (CD9, CD63, CD81, CD109, CD151, CD248, and CD276). Therefore,
the MSC-MV proteome provides a comprehensive basis for understanding
the potential of MSC-MVs to affect tissue repair and regeneration.