title: Subretinal transplantation of forebrain progenitor cells in nonhuman primates: survival and intact retinal function.
abstract: OBJECTIVE
  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.
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon 97239-4197, USA. francisp@ohsu.edu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Francis
authors.forename: Shaomei
authors.initials: S
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Anna
authors.initials: A
authors.lastname: Brown
authors.forename: Thomas
authors.initials: T
authors.lastname: Hwang
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: McFarland
authors.forename: Brett G
authors.initials: BG
authors.lastname: Jeffrey
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: Lynda
authors.initials: L
authors.lastname: Wright
authors.forename: Binoy
authors.initials: B
authors.lastname: Appukuttan
authors.forename: David J
authors.initials: DJ
authors.lastname: Wilson
authors.forename: J Timothy
authors.initials: JT
authors.lastname: Stout
authors.forename: Martha
authors.initials: M
authors.lastname: Neuringer
authors.forename: David M
authors.initials: DM
authors.lastname: Gamm
authors.forename: Raymond D
authors.initials: RD
authors.lastname: Lund
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics; D004596:Electroretinography; D005260:Female; D053686:Fetal Stem Cells / Q000378:metabolism / Q000637:transplantation*; D005451:Fluorescein Angiography; D015870:Gene Expression / Q000502:physiology; D006085:Graft Survival / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008253:Macaca mulatta; D008856:Microscopy, Fluorescence; D051381:Rats; D011922:Rats, Mutant Strains; D012160:Retina / Q000502:physiology*; D012162:Retinal Degeneration / Q000503:physiopathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D014162:Transfection; D014183:Transplantation, Heterologous; D014792:Visual Acuity / Q000502:physiology
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins