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. 2020 Nov 27;11(1):511.
doi: 10.1186/s13287-020-02032-8.

Comprehensive proteomic analysis of exosomes derived from human bone marrow, adipose tissue, and umbilical cord mesenchymal stem cells

Zheng-Gang Wang  1 , Zhi-Yi He  1 , Shuang Liang  1 , Qing Yang  1 , Peng Cheng  2 , An-Min Chen  3
Affiliations

Comprehensive proteomic analysis of exosomes derived from human bone marrow, adipose tissue, and umbilical cord mesenchymal stem cells

Zheng-Gang Wang et al. Stem Cell Res Ther. .

Abstract

Background: Mesenchymal stem cell (MSC)-derived exosomes have shown comprehensive application prospects over the years. Despite performing similar functions, exosomes from different origins present heterogeneous characteristics and components; however, the relative study remains scarce. Lacking of a valuable reference, researchers select source cells for exosome studies mainly based on accessibility and personal preference.

Methods: In this study, exosomes secreted by MSCs derived from different tissues were isolated, by ultracentrifugation, and proteomics analysis was performed. A total of 1014 proteins were detected using a label-free method.

Results: Bioinformatics analysis revealed their shared function in the extracellular matrix receptor. Bone marrow MSC-derived exosomes showed superior regeneration ability, and adipose tissue MSC-derived exosomes played a significant role in immune regulation, whereas umbilical cord MSC-derived exosomes were more prominent in tissue damage repair.

Conclusions: This study systematically and comprehensively analyzes the human MSC-derived exosomes via proteomics, which reveals their potential applications in different fields, so as to provide a reference for researchers to select optimal source cells in future exosome-related studies.

Keywords: Exosomes; Extracellular vesicles; Mesenchymal stem cells; Proteomics; Stem cell-based therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Quality control of MSCs and exosomes. a MSCs were stained with Alizarin red, Oil red O, and Alcian blue to confirm their differentiation into osteogenesis, adipogenesis, and chondrogenesis. (Scale bar 50 μm and 100 μm). b Size distribution of exosomes measured by NTA. c The MSCs and exosomes expression levels of Calnexin, CD9, CD81, and TSG101 were detected via western blot analysis. d TEM images of exosomes derived from MSCs. (Scale bar 100 nm, 500 nm)
Fig. 2
Fig. 2
Bioinformatics analysis of BM-MSC exo. a Venn diagram of BM-MSC-derived exosomes against ExoCarta. b GO analysis of BM-MSC exo. c KEGG analysis of BM-MSC exo
Fig. 3
Fig. 3
Bioinformatics analysis of AT-MSC exo. a Venn diagram of AT-MSC-derived exosomes against ExoCarta. b GO analysis of AT-MSC exo. c KEGG analysis of AT-MSC exo
Fig. 4
Fig. 4
Bioinformatics analysis of UC-MSC exo. a Venn diagram of UC-MSC-derived exosomes against ExoCarta. b GO analysis of UC-MSC exo. c KEGG analysis of UC-MSC exo
Fig. 5
Fig. 5
Horizontal bioinformatics analysis of three sources of exosome proteins. a Venn diagrams of detected proteins in exosomes derived from human MSCs. b GO analysis of the shared proteins among three sources of MSCs. (Red: biological process, green: cellular component, blue: molecular function.) c KEGG analysis of the shared proteins among three sources of MSCs. d Heat map of the protein level of shared proteins among three sources of MSCs. Clusters are assembled by GO analysis. The significantly enriched items are shown on the right
Fig. 6
Fig. 6
Bioinformatics analysis of the specific proteins detected in each source of exosomes. a The volcanogram of differential proteins for BM-MSC exo vs AT-MSC exo, BM-MSC exo vs UC-MSC exo, and AT-MSC exo vs UC-MSC exo. b The cytolocalization of differential proteins for BM-MSC exo vs AT-MSC exo, BM-MSC exo vs UC-MSC exo, and AT-MSC exo vs UC-MSC exo. c GO analysis of specific proteins for each source of exosomes. (Red: biological process, green: cellular component, blue: molecular function). d KEGG analysis of specific proteins for each source of exosomes
Fig. 7
Fig. 7
Membrane protein enrichment in exosomes depends on source cell type. Relative expression of each membrane protein within a sample is depicted on slop charts and membrane protein grouped according to their enrichment or depletion in AT-MSC exo, enrichment in BM-MSC exo, and depletion in UC-MSC exo
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