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 Wilson, J. Timothy Stout, Martha Neuringer, David M. Gamm, Raymond D. Lund

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 - 2009

Fingerprint

Prosencephalon
Primates
Stem Cells
Transplantation
Survival
Green Fluorescent Proteins
Macaca mulatta
Tissue Donors
Retinal Diseases
Aptitude
Temazepam
Operating Rooms
Cell- and Tissue-Based Therapy
Haplorhini
Retina
Rodentia
Outcome Assessment (Health Care)
Inflammation

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Subretinal transplantation of forebrain progenitor cells in nonhuman primates : Survival and intact retinal function. / Francis, Peter J.; Wang, Shaomei; Zhang, Yi; Brown, Anna; Hwang, Thomas; McFarland, Trevor J.; Jeffrey, Brett G.; Lu, Bin; Wright, Lynda; Appukuttan, Binoy; Wilson, David; Timothy Stout, J.; Neuringer, Martha; Gamm, David M.; Lund, Raymond D.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 7, 2009, p. 3425-3431.

Research output: Contribution to journalArticle

Francis, PJ, Wang, S, Zhang, Y, Brown, A, Hwang, T, McFarland, TJ, Jeffrey, BG, Lu, B, Wright, L, Appukuttan, B, Wilson, D, Timothy Stout, J, Neuringer, M, Gamm, DM & Lund, RD 2009, 'Subretinal transplantation of forebrain progenitor cells in nonhuman primates: Survival and intact retinal function', Investigative Ophthalmology and Visual Science, vol. 50, no. 7, pp. 3425-3431. https://doi.org/10.1167/iovs.08-2908
Francis, Peter J. ; Wang, Shaomei ; Zhang, Yi ; Brown, Anna ; Hwang, Thomas ; McFarland, Trevor J. ; Jeffrey, Brett G. ; Lu, Bin ; Wright, Lynda ; Appukuttan, Binoy ; Wilson, David ; Timothy Stout, J. ; Neuringer, Martha ; Gamm, David M. ; Lund, Raymond D. / Subretinal transplantation of forebrain progenitor cells in nonhuman primates : Survival and intact retinal function. In: Investigative Ophthalmology and Visual Science. 2009 ; Vol. 50, No. 7. pp. 3425-3431.
@article{bdfe27d91a15483fa32329b117dfb862,
title = "Subretinal transplantation of forebrain progenitor cells in nonhuman primates: Survival and intact retinal function",
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.",
author = "Francis, {Peter J.} and Shaomei Wang and Yi Zhang and Anna Brown and Thomas Hwang and McFarland, {Trevor J.} and Jeffrey, {Brett G.} and Bin Lu and Lynda Wright and Binoy Appukuttan and David Wilson and {Timothy Stout}, J. and Martha Neuringer and Gamm, {David M.} and Lund, {Raymond D.}",
year = "2009",
doi = "10.1167/iovs.08-2908",
language = "English (US)",
volume = "50",
pages = "3425--3431",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "7",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=67649995736&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649995736&partnerID=8YFLogxK

U2 - 10.1167/iovs.08-2908

DO - 10.1167/iovs.08-2908

M3 - Article

C2 - 19234356

AN - SCOPUS:67649995736

VL - 50

SP - 3425

EP - 3431

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 7

ER -