TY - JOUR
T1 - Subretinal transplantation of forebrain progenitor cells in nonhuman primates
T2 - Survival and intact retinal function
AU - Francis, Peter J.
AU - Wang, Shaomei
AU - Zhang, Yi
AU - Brown, Anna
AU - Hwang, Thomas
AU - McFarland, Trevor J.
AU - Jeffrey, Brett G.
AU - Lu, Bin
AU - Wright, Lynda
AU - Appukuttan, Binoy
AU - Wilson, David J.
AU - Timothy Stout, J.
AU - Neuringer, Martha
AU - Gamm, David M.
AU - Lund, Raymond D.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1167/iovs.08-2908
DO - 10.1167/iovs.08-2908
M3 - Article
C2 - 19234356
AN - SCOPUS:67649995736
SN - 0146-0404
VL - 50
SP - 3425
EP - 3431
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 7
ER -