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First published online September 28, 2006
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2006-0444v1
25/1/197    most recent
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Submitted on July 19, 2006
Accepted on September 19, 2006

Technology Development

N-glycolylneuraminic acid xenoantigen contamination of human embryonic and mesenchymal stem cells is substantially reversible

Annamari Heiskanen 1, Tero Satomaa 1, Sari Tiitinen 2, Anita Laitinen 2, Sirkka Mannelin 2, Ulla Impola 2, Milla Mikkola 3, Cia Olsson 4, Halina Miller-Podraza 5, Maria Blomqvist 1, Anne Olonen 1, Hanna Salo 1, Petri Lehenkari 6, Timo Tuuri 4, Timo Otonkoski 7, Jari Natunen 1, Juhani Saarinen 1, Jarmo Laine 2*

1 Glykos Finland Ltd., Helsinki, Finland
2 Finnish Red Cross Blood Service, Helsinki, Finland
3 Biomedicum Helsinki, Program of Developmental and Reproductive Biology, University of Helsinki, Finland
4 Biomedicum Helsinki, Program of Developmental and Reproductive Biology, University of Helsinki, Finland; Family Federation of Finland, Infertility Clinic, Helsinki, Finland
5 Institute of Biomedicine, Department of Medical Chemistry and Cell Biology, University of Göteborg, Sweden
6 Department of Surgery, Clinical Research Center, University of Oulu, Finland
7 Biomedicum Helsinki, Program of Developmental and Reproductive Biology, University of Helsinki, Finland; Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland

* To whom correspondence should be addressed. E-mail: jarmo.laine{at}veripalvelu.fi.


  Abstract

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 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, 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 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.

While 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.

 Key Words. stem cell, xenoantigen, Neu5Gc, clinical trial




This article has been cited by other articles:


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 Stem CellsHome page
F. Mannello and G. A. Tonti
Concise Review: No Breakthroughs for Human Mesenchymal and Embryonic Stem Cell Culture: Conditioned Medium, Feeder Layer, or Feeder-Free; Medium with Fetal Calf Serum, Human Serum, or Enriched Plasma; Serum-Free, Serum Replacement Nonconditioned Medium, or Ad Hoc Formula? All That Glitters Is Not Gold!
Stem Cells, July 1, 2007; 25(7): 1603 - 1609.
[Abstract] [Full Text] [PDF]


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