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

Gamm Lab // Publications // Jul 01 2009

PubMed ID: 19234356

Author(s): Francis PJ, Wang S, Zhang Y, Brown A, Hwang T, McFarland TJ, Jeffrey BG, Lu B, Wright L, Appukuttan B, Wilson DJ, Stout JT, Neuringer M, Gamm DM, Lund RD. Subretinal transplantation of forebrain progenitor cells in nonhuman primates: survival and intact retinal function. Invest Ophthalmol Vis Sci. 2009 Jul;50(7):3425-31. doi: 10.1167/iovs.08-2908. Epub 2009 Feb 21. PMID 19234356

Journal: Investigative Ophthalmology & Visual Science, Volume 50, Issue 7, Jul 2009

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 (hNPC(ctx)) introduced into the subretinal space of normal rhesus macaques.

METHODS hNPC(ctx) transduced with green fluorescent protein (hNPC(ctx)-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, hNPC(ctx)-GFP from the same batch were also injected into Royal College of Surgeons (RCS) rats and compared with nonlabeled hNPC(ctx).

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.