Document Detail

Proteomic profiling of human embryonic stem cell-derived microvesicles reveals a risk of transfer of proteins of bovine and mouse origin.
MedLine Citation:
PMID:  19401887     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AIMS: Microvesicles (MV) shed from the plasma membrane of eukaryotic cells, including human embryonic stem cells (hESC), contain proteins, lipids and RNA and serve as mediators of cell-to-cell communication. However, they may also contain immunogenic membrane domains and infectious particles acquired from xenogenic components of the culture milieu. Therefore, MV represent a potential risk for clinical application of cell therapy. METHODS: We tested the ability of hESC and their most commonly used feeder cells, mouse embryonic fibroblasts (MEF), to produce MV. We found that hESC are potent producers of MV, whereas mitotically inactivated MEF do not produce any detectable MV. We therefore employed a combined proteomic approach to identify the molecules that constitute the major components of MV from hESC maintained in a standard culture setting with xenogenic feeder cells. RESULTS: In purified MV fractions, we identified a total of 22 proteins, including five unique protein species that are known to be highly expressed in invasive cancers and participate in cellular activation, metastasis and inhibition of apoptosis. Moreover, we found that hESC-derived MV contained the immunogenic agents apolipoprotein and transferrin, a source of Neu5Gc, as well as mouse retroviral Gag protein. CONCLUSIONS: These findings indicate that MV represent a mechanism by which hESC communicate; however, they also serve as potential carriers of immunogenic and pathogenic compounds acquired from environment. Our results highlight a potential danger regarding the use of hESC that have previously been exposed to animal proteins and cells.
I Kubikova; H Konecna; O Sedo; Z Zdrahal; P Rehulka; H Hribkova; H Rehulkova; A Hampl; J Chmelik; P Dvorak
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cytotherapy     Volume:  11     ISSN:  1477-2566     ISO Abbreviation:  Cytotherapy     Publication Date:  2009  
Date Detail:
Created Date:  2009-04-29     Completed Date:  2009-11-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100895309     Medline TA:  Cytotherapy     Country:  England    
Other Details:
Languages:  eng     Pagination:  330-40, 1 p following 340     Citation Subset:  IM    
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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MeSH Terms
Antigens, Heterophile / immunology*
Antigens, Neoplasm / immunology,  metabolism
Apolipoproteins / immunology,  metabolism
Apoptosis Regulatory Proteins / immunology,  metabolism
Cell Line
Cell-Derived Microparticles / immunology*,  metabolism
Coculture Techniques
Embryonic Stem Cells / cytology,  immunology,  metabolism*
Fibroblasts / cytology,  immunology,  metabolism*
Gene Products, gag / immunology,  metabolism
Microscopy, Electron
Tandem Mass Spectrometry
Tissue Therapy / adverse effects
Transferrin / immunology,  metabolism
Reg. No./Substance:
0/Antigens, Heterophile; 0/Antigens, Neoplasm; 0/Apolipoproteins; 0/Apoptosis Regulatory Proteins; 0/Gene Products, gag; 11096-37-0/Transferrin

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