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.
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References
Barker, R.A. et al. Cell Transplant. 9, 235–246 (2000).
Brundin, P. et al. Exp. Brain Res. 70, 192–208 (1988).
Pakzaban, P. et al. Neuroscience 62, 989–1001 (1994).
Frodl, E.M. et al. Brain Res. 647, 286–298 (1994).
Grasbon-Frodl, E.M. et al. Neuroscience 73, 171–183 (1996).
Pundt, L.L. et al. Brain Res. Bull. 39, 23–32 (1996).
Stromberg, I. et al. Brain Res. Bull. 38, 221–233 (1995).
Lund, R.D. et al. in Neural Transplantation: A Practical Approach (eds. Dunnett, S.B. & Bjorklund, A.) 161–176 (Oxford University Press, Oxford, 1992).
Pedersen, E.B. et al. Exp. Brain Res. 106, 181–186 (1995).
Stromberg, I. et al. J. Neurosci. 9, 614–624 (1989).
Armstrong, R.J. et al. Exp. Neurol. 175, 98–111 (2002).
Armstrong, R.J. et al. Exp. Brain Res. 151, 204–217 (2003).
Zietlow, R. et al. J. Anat. 207, 227–240 (2005).
Joannides, A.J. et al. Stem Cells 25, 731–737 (2007).
Brundin, P. et al. Cell Transplant. 9, 179–195 (2000).
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.
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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.
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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
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DOI: https://doi.org/10.1038/nmeth.1308
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