T.J.M., B.C., R.D.L. and A.C. contributed equally to this work.
Transplantation of human central nervous system stem cells – neuroprotection in retinal degeneration
Version of Record online: 25 JAN 2012
© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 35, Issue 3, pages 468–477, February 2012
How to Cite
McGill, T. J., Cottam, B., Lu, B., Wang, S., Girman, S., Tian, C., Huhn, S. L., Lund, R. D. and Capela, A. (2012), Transplantation of human central nervous system stem cells – neuroprotection in retinal degeneration. European Journal of Neuroscience, 35: 468–477. doi: 10.1111/j.1460-9568.2011.07970.x
- Issue online: 31 JAN 2012
- Version of Record online: 25 JAN 2012
- Received 13 October 2011, revised 18 November 2011, accepted 21 November 2011
- RCS rat;
- stem cell;
Stem cells derived from the human brain and grown as neurospheres (HuCNS-SC) have been shown to be effective in treating central neurodegenerative conditions in a variety of animal models. Human safety data in neurodegenerative disorders are currently being accrued. In the present study, we explored the efficacy of HuCNS-SC in a rodent model of retinal degeneration, the Royal College of Surgeons (RCS) rat, and extended our previous cell transplantation studies to include an in-depth examination of donor cell behavior and phenotype post-transplantation. As a first step, we have shown that HuCNS-SC protect host photoreceptors and preserve visual function after transplantation into the subretinal space of postnatal day 21 RCS rats. Moreover, cone photoreceptor density remained relatively constant over several months, consistent with the sustained visual acuity and luminance sensitivity functional outcomes. The novel findings of this study include the characterization and quantification of donor cell radial migration from the injection site and within the subretinal space as well as the demonstration that donor cells maintain an immature phenotype throughout the 7 months of the experiment and undergo very limited proliferation with no evidence of uncontrolled growth or tumor-like formation. Given the efficacy findings and lack of adverse events in the RCS rat in combination with the results from ongoing clinical investigations, HuCNS-SC appear to be a well-suited candidate for cell therapy in retinal degenerative conditions.