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<sup>*‡¶∥

†</sup>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.

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