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TECHNOLOGY DEVELOPMENT

N-Glycolylneuraminic Acid Xenoantigen Contamination of Human Embryonic and Mesenchymal Stem Cells Is Substantially Reversible

^aGlykos Finland Ltd., Helsinki, Finland;
^bFinnish Red Cross Blood Service, Helsinki, Finland;
^cBiomedicum Helsinki, University of Helsinki, Finland;
^dFamily Federation of Finland, Infertility Clinic, Helsinki, Finland;
^eInstitute of Biomedicine, Department of Medical Chemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden;
^fDepartment of Surgery, Clinical Research Center, University of Oulu, Oulu, Finland;
^gHospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland

Key Words. Stem cell • Xenoantigen • N-Glycolylneuraminic acid • Clinical trial

Correspondence: Jarmo Laine, M.D., Ph.D., Department of Research and Development, Finnish Red Cross Blood Service, Kivihaantie 7, 00310 Helsinki, Finland. Telephone: +358 9 580 1583; Fax: +358 9 580 1233; e-mail: jarmo.laine{at}veripalvelu.fi

Received July 19, 2006; accepted for publication September 19, 2006.
First published online in STEM CELLS EXPRESS   September 28, 2006.



Human embryonic and mesenchymal stem cell therapies may offer significant benefit to a large number of patients. Recently, however, human embryonic stem cell lines cultured on mouse feeder cells were reported to be contaminated by the xeno-carbohydrate N-glycolylneuraminic acid (Neu5Gc) and considered potentially unfit for human therapy. To determine the extent of the problem of Neu5Gc contamination for the development of stem cell therapies, we investigated whether it also occurs in cells cultured on human feeder cells and in mesenchymal stem cells, what are the sources of contamination, and whether the contamination is reversible. We found that N-glycolylneuraminic acid was present in embryonic stem cells cultured on human feeder cells, correlating with the presence of Neu5Gc in components of the commercial serum replacement culture medium. Similar contamination occurred in mesenchymal stem cells cultured in the presence of fetal bovine serum. The results suggest that the Neu5Gc is present in both glycoprotein and lipid-linked glycans, as detected by mass spectrometric analysis and monoclonal antibody staining, respectively. Significantly, the contamination was largely reversible in the progeny of both cell types, suggesting that decontaminated cells may be derived from existing stem cell lines. Although major complications have not been reported in the clinical trials with mesenchymal stem cells exposed to fetal bovine serum, the immunogenic contamination may potentially be reflected in the viability and efficacy of the transplanted cells and thus bias the published results. Definition of safe culture conditions for stem cells is essential for future development of cellular therapies.

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