Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Neonatal desensitization allows long-term survival of neural xenotransplants without immunosuppression

Abstract

Preclinical development of human cells for potential therapeutic application in neurodegenerative diseases requires that their long-term survival, stability and functional efficacy be studied in animal models of human disease. Here we describe a strategy for long-term immune protection of human fetal and stem cell–derived neural cells transplanted into the adult rat brain, by desensitizing the host rat to similar cells in the neonatal period, without the need for additional immunosuppression.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Representative photomicrographs of hPF cells transplanted into the adult rat striatum.

References

  1. Barker, R.A. et al. Cell Transplant. 9, 235–246 (2000).

    Article  CAS  Google Scholar 

  2. Brundin, P. et al. Exp. Brain Res. 70, 192–208 (1988).

    CAS  PubMed  Google Scholar 

  3. Pakzaban, P. et al. Neuroscience 62, 989–1001 (1994).

    Article  CAS  Google Scholar 

  4. Frodl, E.M. et al. Brain Res. 647, 286–298 (1994).

    Article  CAS  Google Scholar 

  5. Grasbon-Frodl, E.M. et al. Neuroscience 73, 171–183 (1996).

    Article  CAS  Google Scholar 

  6. Pundt, L.L. et al. Brain Res. Bull. 39, 23–32 (1996).

    Article  CAS  Google Scholar 

  7. Stromberg, I. et al. Brain Res. Bull. 38, 221–233 (1995).

    Article  CAS  Google Scholar 

  8. Lund, R.D. et al. in Neural Transplantation: A Practical Approach (eds. Dunnett, S.B. & Bjorklund, A.) 161–176 (Oxford University Press, Oxford, 1992).

    Google Scholar 

  9. Pedersen, E.B. et al. Exp. Brain Res. 106, 181–186 (1995).

    Article  CAS  Google Scholar 

  10. Stromberg, I. et al. J. Neurosci. 9, 614–624 (1989).

    Article  CAS  Google Scholar 

  11. Armstrong, R.J. et al. Exp. Neurol. 175, 98–111 (2002).

    Article  Google Scholar 

  12. Armstrong, R.J. et al. Exp. Brain Res. 151, 204–217 (2003).

    Article  Google Scholar 

  13. Zietlow, R. et al. J. Anat. 207, 227–240 (2005).

    Article  CAS  Google Scholar 

  14. Joannides, A.J. et al. Stem Cells 25, 731–737 (2007).

    Article  CAS  Google Scholar 

  15. Brundin, P. et al. Cell Transplant. 9, 179–195 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank P. Morgan and A. Gallimore for advice and guidance with immunology experiments, H. Hemmings (Cornell University) for the generous gift of antibody to DARPP-32, T. Hayes for help with acquiring confocal imaging, and A. Heuer for assistance with assembling the images. These studies were supported by the UK Medical Research Council, the Lister Institute of Preventive Medicine and EU FP6 project funding.

Author information

Authors and Affiliations

Authors

Contributions

C.M.K. and S.V.P. carried out all experiments. C.S., R.P. and N.N.A. procured the human tissue. A.B. and N.D.A. prepared human embryonic stem cells. C.M.K. wrote the manuscript with S.B.D. and A.E.R., who supervised the project.

Corresponding author

Correspondence to Claire M Kelly.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–2, Supplementary Methods (PDF 244 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kelly, C., Precious, S., Scherf, C. et al. Neonatal desensitization allows long-term survival of neural xenotransplants without immunosuppression. Nat Methods 6, 271–273 (2009). https://doi.org/10.1038/nmeth.1308

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth.1308

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing