A comprehensive proteomics profiling identifies NRP1 as a novel identity marker of human bone marrow mesenchymal stromal cell-derived small extracellular vesicles.
Human bone marrow-derived mesenchymal stromal cells
Identity marker
Paracrine effectors
Pathway enrichment
Proteomics
Small extracellular vesicles
Journal
Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581
Informations de publication
Date de publication:
18 12 2019
18 12 2019
Historique:
received:
30
07
2019
accepted:
28
11
2019
revised:
05
11
2019
entrez:
20
12
2019
pubmed:
20
12
2019
medline:
25
7
2020
Statut:
epublish
Résumé
Clinical applications have shown extracellular vesicles (EVs) to be a major paracrine effector in therapeutic responses produced by human mesenchymal stromal/stem cells (hMSCs). As the regenerative capacity of EVs is mainly ascribed to the transfer of proteins and RNA composing its cargo, and to the activity attributed by the protein surface markers, we sought to profile the protein composition of small EVs released from hMSCs to identify hMSC-EV biomarkers with potential clinical relevance. Small EVs were produced and qualified from five human bone marrow MSC donors at low passage following a 48-h culture in exosome-depleted medium further processed by steps of centrifugation, filtration, and precipitation. Quantitative proteomic analysis comparing the protein profile of the EVs released from hMSCs and their parental cell was conducted using tandem mass tag labeling combined to mass spectrometry (LC-MS/MS) to identify enriched EV protein markers. Nanoparticle tracking analysis showed no differences in the EV concentration and size among the five hMSC donors (1.83 × 10 The identification and verification of NRP1 as a novel enriched surface marker from multiple batches of EVs derived from multiple hMSC donors may serve as a biomarker for the assessment and measurement of EVs for therapeutic uses.
Sections du résumé
BACKGROUND
Clinical applications have shown extracellular vesicles (EVs) to be a major paracrine effector in therapeutic responses produced by human mesenchymal stromal/stem cells (hMSCs). As the regenerative capacity of EVs is mainly ascribed to the transfer of proteins and RNA composing its cargo, and to the activity attributed by the protein surface markers, we sought to profile the protein composition of small EVs released from hMSCs to identify hMSC-EV biomarkers with potential clinical relevance.
METHODS
Small EVs were produced and qualified from five human bone marrow MSC donors at low passage following a 48-h culture in exosome-depleted medium further processed by steps of centrifugation, filtration, and precipitation. Quantitative proteomic analysis comparing the protein profile of the EVs released from hMSCs and their parental cell was conducted using tandem mass tag labeling combined to mass spectrometry (LC-MS/MS) to identify enriched EV protein markers.
RESULTS
Nanoparticle tracking analysis showed no differences in the EV concentration and size among the five hMSC donors (1.83 × 10
CONCLUSION
The identification and verification of NRP1 as a novel enriched surface marker from multiple batches of EVs derived from multiple hMSC donors may serve as a biomarker for the assessment and measurement of EVs for therapeutic uses.
Identifiants
pubmed: 31852509
doi: 10.1186/s13287-019-1516-2
pii: 10.1186/s13287-019-1516-2
pmc: PMC6921509
doi:
Substances chimiques
Biomarkers
0
Tetraspanin 30
0
Neuropilin-1
144713-63-3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
401Références
Int J Exp Pathol. 2012 Apr;93(2):81-103
pubmed: 22414290
Hepatology. 2008 May;47(5):1634-43
pubmed: 18395843
J Neurosci Res. 2012 Sep;90(9):1794-802
pubmed: 22535477
PLoS One. 2007 Sep 26;2(9):e941
pubmed: 17895982
Blood. 2008 Feb 15;111(4):2036-45
pubmed: 18065694
J Extracell Vesicles. 2019 Apr 29;8(1):1609206
pubmed: 31069028
Stem Cells Dev. 2013 Oct 1;22(19):2606-18
pubmed: 23676112
Cell Stem Cell. 2011 Jul 8;9(1):11-5
pubmed: 21726829
Cells. 2018 Aug 01;7(8):null
pubmed: 30071693
Cancer Sci. 2018 Aug;109(8):2364-2374
pubmed: 29908100
Adv Anat Pathol. 2019 Jan;26(1):69-74
pubmed: 30339548
J Chromatogr A. 2014 Dec 5;1371:125-35
pubmed: 25458527
Leukemia. 2014 Apr;28(4):970-3
pubmed: 24445866
Arthritis Res Ther. 2014;16(5):432
pubmed: 25606595
J Extracell Vesicles. 2015 Dec 31;4:30087
pubmed: 26725829
Oncotarget. 2016 Apr 12;7(15):19709-22
pubmed: 26919098
Front Immunol. 2016 Jul 26;7:282
pubmed: 27507971
Stem Cell Rev Rep. 2017 Apr;13(2):244-257
pubmed: 28054239
Cytotherapy. 2006;8(4):315-7
pubmed: 16923606
Biochem J. 2010 Mar 15;427(1):29-40
pubmed: 20102335
Cell Transplant. 2018 Jul;27(7):1080-1095
pubmed: 29954220
Stem Cells Dev. 2019 Mar 15;28(6):398-409
pubmed: 30638129
PLoS One. 2012;7(6):e38746
pubmed: 22723882
Cell Stem Cell. 2009 Jul 2;5(1):54-63
pubmed: 19570514
Mol Ther. 2009 Nov;17(11):1938-47
pubmed: 19690521
Front Immunol. 2018 Jun 13;9:1326
pubmed: 29951064
Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):E968-77
pubmed: 26858453
Biomedicine. 1977 Dec;27(9-10):344-9
pubmed: 606310
J Extracell Vesicles. 2015 May 14;4:27066
pubmed: 25979354
Stem Cell Res. 2007 Nov;1(2):129-37
pubmed: 19383393
Nat Rev Immunol. 2009 Aug;9(8):581-93
pubmed: 19498381
J Extracell Vesicles. 2018 Nov 23;7(1):1535750
pubmed: 30637094
J Trauma Acute Care Surg. 2012 Nov;73(5):1161-7
pubmed: 22976425
Annu Rev Pharmacol Toxicol. 2015;55:439-464
pubmed: 25292428
J Control Release. 2017 Sep 28;262:247-258
pubmed: 28687495
Gut. 2012 Jun;61(6):894-906
pubmed: 21997562
Tissue Eng Part A. 2013 Jan;19(1-2):24-9
pubmed: 22839964
Stem Cell Res. 2011 May;6(3):206-14
pubmed: 21419744
Cell Stem Cell. 2018 Jun 01;22(6):824-833
pubmed: 29859173
Med Hypotheses. 1995 Nov;45(5):486-90
pubmed: 8748093
Biomed Res Int. 2014;2014:965849
pubmed: 25530971
Nephrol Dial Transplant. 2012 Aug;27(8):3037-42
pubmed: 22851627
J Extracell Vesicles. 2015 Jul 17;4:27031
pubmed: 26194179
Biomed Res Int. 2018 Jan 30;2018:8545347
pubmed: 29662902
PLoS One. 2012;7(10):e47559
pubmed: 23133515
Regen Med. 2011 Jul;6(4):481-92
pubmed: 21749206
Exp Ther Med. 2018 May;15(5):4067-4079
pubmed: 29725359
J Surg Res. 2013 Aug;183(2):907-15
pubmed: 23522455