Proteomic Analysis of Microvesicles Derived from Human Mesenchymal Stem Cells

被引:312
作者
Kim, Han-Soo [3 ,4 ]
Choi, Do-Young [7 ]
Yun, So Jeong [1 ]
Choi, Seong-Mi [5 ]
Kang, Jeong Won [7 ]
Jung, Jin Woo [7 ]
Hwang, Daehee [1 ,2 ]
Kim, Kwang Pyo [7 ]
Kim, Dong-Wook [4 ,5 ,6 ]
机构
[1] POSTECH, Sch Interdisciplinary Biosci & Bioengn, Pohang 790784, South Korea
[2] POSTECH, Dept Chem Engn, Pohang 790784, South Korea
[3] Yonsei Univ, Coll Med, Dept Lab Med, Seoul 120752, South Korea
[4] Yonsei Univ, Coll Med, Cell Therapy Ctr, Seoul 120752, South Korea
[5] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul 120752, South Korea
[6] Yonsei Univ, Coll Med, Dept Physiol, Seoul 120752, South Korea
[7] Konkuk Univ, WCU Program, Dept Mol Biotechnol, Seoul 143701, South Korea
关键词
mesenchymal stem cells; microvesicle; proteomics; self-renewal; tissue regeneration; STROMAL CELLS; GROWTH-FACTOR; PROGENITOR CELLS; SELF-RENEWAL; CANCER; DIFFERENTIATION; PROLIFERATION; MIGRATION; MICROPARTICLES; EXOSOMES;
D O I
10.1021/pr200682z
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:839 / 849
页数:11
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