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Complement targeting of nonhuman sialic acid does not mediate cell death of human embryonic stem cells

Nature Medicine volume 12, pages 1113–1114 (2006)Cite this article

To the editor:

Human embryonic stem cells (HESCs) represent a promising cell source to replace damaged or diseased tissue. However, the recent observation that one of the US federally approved HESC lines1 contains a potentially immunogenic nonhuman sialic acid, Neu5Gc (ref. 2), indicates that there may be limitations on their use. Neu5Gc is found on the surface of most nonhuman mammalian cells and is targeted by circulating antibodies found in human sera, which results in complement-mediated death of cells bearing this molecule3. Based on this report2, a broader investigation of HESC lines and human sera is required to determine the extent of Neu5Gc incorporation and the subsequent likelihood of HESC cell death induced by recipient sera.

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Figure 1: Flow cytometric analysis of HESC and MEF cell death in response to sera.

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Acknowledgements

This work was supported by research grants to M.B. from the Canadian Institutes of Health Research and the National Cancer Research Institute of Canada.

Author information

Author notes

  1. Chantal Cerdan and Sean C Bendall: These authors contributed equally to this work.

Authors and Affiliations

  1. McMaster Cancer and Stem Cell Biology Research Institute, Michael G. DeGroote School of Medicine, McMaster University, 1200 Main Street, MDCL, Hamilton, L9G 4N6, Ontario, Canada

    Chantal Cerdan, Sean C Bendall, Morag Stewart, Tamra Werbowetski & Mickie Bhatia

  2. Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, 1151 Richmond Street, London, N6A 5C1, Ontario, Canada

    Sean C Bendall

  3. Robarts Research Institute, Krembil Centre for Stem Cell Biology and Regenerative Medicine, 100 Perth Drive, London, N6A 5K8, Ontario, Canada

    Lisheng Wang

  4. Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, L8N 3Z5, Ontario, Canada

    Morag Stewart & Mickie Bhatia

Authors
  1. Chantal Cerdan
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  2. Sean C Bendall
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  3. Lisheng Wang
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  5. Tamra Werbowetski
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Supplementary information

Supplementary Fig. 1

Effect of heat inactivation of serum exposed to HESC lines and MEFs compared to PBS (no serum) control. (PDF 281 kb)

Supplementary Fig. 2

Binding of complement C3 from human sera to HESCs and MEFs (PDF 510 kb)

Supplementary Fig. 3

Binding of complement C3 from human serum to mixed populations of HESCs (GFP+ H9) and MEFs exposed or not to serum. (PDF 645 kb)

Supplementary Table 1

Neu5Gc content from HESC culture media and MEFs (PDF 72 kb)

Supplementary Methods (PDF 61 kb)

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Cerdan, C., Bendall, S., Wang, L. et al. Complement targeting of nonhuman sialic acid does not mediate cell death of human embryonic stem cells. Nat Med 12, 1113–1114 (2006). https://doi.org/10.1038/nm1006-1113

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