Subretinal transplantation of forebrain progenitor cells in nonhuman primates: Survival and intact retinal function

Peter J. Francis, Shaomei Wang, Yi Zhang, Anna Brown, Thomas Hwang, Trevor J. McFarland, Brett G. Jeffrey, Bin Lu, Lynda Wright, Binoy Appukuttan, David J. Wilson, J. Timothy Stout, Martha Neuringer, David M. Gamm, Raymond D. Lund

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29 Scopus citations

Abstract

PURPOSE. Cell-based therapy rescues retinal structure and function in rodent models of retinal disease, but translation to clinical practice will require more information about the consequences of transplantation in an eye closely resembling the human eye. The authors explored donor cell behavior using human cortical neural progenitor cells (hNPCctx) introduced into the subretinal space of normal rhesus macaques. METHODS. hNPCctx transduced with green fluorescent protein (hNPCctx-GFP) were delivered bilaterally into the subretinal space of six normal adult rhesus macaques under conditions paralleling those of the human operating room. Outcome measures included clinical parameters of surgical success, multifocal electroretinogram (mfERG), and histopathologic analyses performed between 3 and 39 days after engraftment. To test the effects of GFP transduction on cell bioactivity, hNPCctx-GFP from the same batch were also injected into Royal College of Surgeons (RCS) rats and compared with nonlabeled hNPCctx.RESULTS. Studies using RCS rats indicated that GFP transduction did not alter the ability of the cells to rescue vision. After cells were introduced into the monkey subretinal space by a pars plana transvitreal approach, the resultant detachment was rapidly resolved, and retinal function showed little or no disturbance in mfERG recordings. Retinal structure was unaffected and no signs of inflammation or rejection were seen. Donor cells survived as a single layer in the subretinal space, and no cells migrated into the inner retina. CONCLUSIONS. Human neural progenitor cells can be introduced into a primate eye without complication using an approach that would be suitable for extrapolation to human patients.

Original languageEnglish (US)
Pages (from-to)3425-3431
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number7
DOIs
StatePublished - Dec 1 2009

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ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Francis, P. J., Wang, S., Zhang, Y., Brown, A., Hwang, T., McFarland, T. J., Jeffrey, B. G., Lu, B., Wright, L., Appukuttan, B., Wilson, D. J., Timothy Stout, J., Neuringer, M., Gamm, D. M., & Lund, R. D. (2009). Subretinal transplantation of forebrain progenitor cells in nonhuman primates: Survival and intact retinal function. Investigative Ophthalmology and Visual Science, 50(7), 3425-3431. https://doi.org/10.1167/iovs.08-2908