Authors: Kubikova, I.¹; Konecna, H.²; Sedo, O.²; Zdrahal, Z.²; Rehulka, P.³; Hribkova, H.¹; Rehulkova, H.³; Hampl, A.⁴; Chmelik, J.³; Dvorak, P.⁴

Source: Cytotherapy, Volume 11, Number 3, May 2009 , pp. 330-340(11)

Publisher: Informa Healthcare

Abstract:

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.

Keywords: Cell-to-cell communication; horizontal transfer of immunogenic and pathogenic; human embryonic stem cells; membrane-derived microvesicles; proteomics

Document Type: Research article

DOI: http://dx.doi.org/10.1080/14653240802595531

Affiliations: 1: Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic 2: Department of Functional Genomics and Proteomics, Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic 3: Institute of Analytical Chemistry, Academy of Sciences of the Czech Republic, Brno, Czech Republic 4: Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic,Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Brno, Czech Republic

Publication date: 2009-05-01

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