Proteomic Analysis of Microvesicles Derived from Human Mesenchymal Stem Cells
 Authors and Affiliations
 Authors and Affiliations
Han-Soo Kim†‡◆, Do-Young Choi§◆, So Jeong Yun⊥◆, Seong-Mi Choi¶, Jeong Won Kang§, Jin Woo Jung§, Daehee Hwang*⊥#∇, Kwang Pyo Kim*§, and Dong-Wook Kim*‡¶∥
†Department of Laboratory Medicine, ‡Cell Therapy Center, ¶Severance Biomedical Science Institute, and ∥Department of Physiology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemoon-gu, Seoul 120-752, Republic of Korea
§ Department of Molecular Biotechnology, WCU Program, Konkuk University, Seoul, 143-701, Republic of Korea
⊥School of Interdisciplinary Bioscience and Bioengineering, #Department of Chemical Engineering, and ∇Integrative Bioscience and Biotechnology, POSTECH, Pohang, 790-784, Republic of Korea
*Corresponding Author
Author Contributions ◆These authors contributed equally to this manuscript.
Abstract 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.
Keywords: mesenchymal stem cells; microvesicle; proteomics; self-renewal; tissue regeneration
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