Allogeneic iPSC-derived RPE cell graft failure following transplantation into the subretinal space in nonhuman primates

Trevor McGill, Jonathan Stoddard, Auren M. Renner, Ilhem Messaoudi, Kapil Bharti, Shoukhrat Mitalipov, Andreas (Andy) Lauer, David Wilson, Martha Neuringer

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

PURPOSE. To characterize the intraocular immune response following transplantation of iPSderived allogeneic RPE cells into the subretinal space of non–immune-suppressed rhesus macaques. METHODS. GFP-labeled allogeneic iPS-derived RPE cells were transplanted into the subretinal space of one eye (n = 6), and into the contralateral eye 1 day to 4 weeks later, using a twostage transretinal and transscleral approach. Retinas were examined pre- and post-surgery by color fundus photography, fundus autofluorescence, and optical coherence tomography (OCT) imaging. Animals were euthanized between 2 hours and 7 weeks following transplantation. T-cell (CD3), B-cell (CD20), and microglial (Iba1) responses were assessed immunohistochemically. RESULTS. Cells were delivered into the subretinal space in all eyes without leakage into the vitreous. Transplanted RPE cells were clearly visible at 4 days after surgery but were no longer detectable by 3 weeks. In localized areas within the bleb containing transplanted cells, T- and B-cell infiltrates and microglia were observed in the subretinal space and underlying choroid. A T-cell response predominated at 4 days, but converted to a B-cell response at 3 weeks. By 7 weeks, few infiltrates or microglia remained. Host RPE and choroid were disrupted in the immediate vicinity of the graft, with fibrosis in the subretinal space. CONCLUSIONS. Engraftment of allogeneic RPE cells failed following transplantation into the subretinal space of rhesus macaques, likely due to rejection by the immune system. These data underscore the need for autologous cell sources and/or confirmation of adequate immune suppression to ensure survival of transplanted RPE cells.

Original languageEnglish (US)
Pages (from-to)1374-1383
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume59
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Primates
Transplantation
Transplants
B-Lymphocytes
Choroid
Microglia
Macaca mulatta
T-Lymphocytes
Photography
Homologous Transplantation
Optical Coherence Tomography
Blister
Ambulatory Surgical Procedures
Retina
Immune System
Fibrosis
Color

Keywords

  • Allogeneic RPE
  • Cell transplantation
  • Graft failure

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Allogeneic iPSC-derived RPE cell graft failure following transplantation into the subretinal space in nonhuman primates. / McGill, Trevor; Stoddard, Jonathan; Renner, Auren M.; Messaoudi, Ilhem; Bharti, Kapil; Mitalipov, Shoukhrat; Lauer, Andreas (Andy); Wilson, David; Neuringer, Martha.

In: Investigative Ophthalmology and Visual Science, Vol. 59, No. 3, 01.03.2018, p. 1374-1383.

Research output: Contribution to journalArticle

@article{e5ac3d0fe754452eaafac9e7bd46c3ec,
title = "Allogeneic iPSC-derived RPE cell graft failure following transplantation into the subretinal space in nonhuman primates",
abstract = "PURPOSE. To characterize the intraocular immune response following transplantation of iPSderived allogeneic RPE cells into the subretinal space of non–immune-suppressed rhesus macaques. METHODS. GFP-labeled allogeneic iPS-derived RPE cells were transplanted into the subretinal space of one eye (n = 6), and into the contralateral eye 1 day to 4 weeks later, using a twostage transretinal and transscleral approach. Retinas were examined pre- and post-surgery by color fundus photography, fundus autofluorescence, and optical coherence tomography (OCT) imaging. Animals were euthanized between 2 hours and 7 weeks following transplantation. T-cell (CD3), B-cell (CD20), and microglial (Iba1) responses were assessed immunohistochemically. RESULTS. Cells were delivered into the subretinal space in all eyes without leakage into the vitreous. Transplanted RPE cells were clearly visible at 4 days after surgery but were no longer detectable by 3 weeks. In localized areas within the bleb containing transplanted cells, T- and B-cell infiltrates and microglia were observed in the subretinal space and underlying choroid. A T-cell response predominated at 4 days, but converted to a B-cell response at 3 weeks. By 7 weeks, few infiltrates or microglia remained. Host RPE and choroid were disrupted in the immediate vicinity of the graft, with fibrosis in the subretinal space. CONCLUSIONS. Engraftment of allogeneic RPE cells failed following transplantation into the subretinal space of rhesus macaques, likely due to rejection by the immune system. These data underscore the need for autologous cell sources and/or confirmation of adequate immune suppression to ensure survival of transplanted RPE cells.",
keywords = "Allogeneic RPE, Cell transplantation, Graft failure",
author = "Trevor McGill and Jonathan Stoddard and Renner, {Auren M.} and Ilhem Messaoudi and Kapil Bharti and Shoukhrat Mitalipov and Lauer, {Andreas (Andy)} and David Wilson and Martha Neuringer",
year = "2018",
month = "3",
day = "1",
doi = "10.1167/iovs.17-22467",
language = "English (US)",
volume = "59",
pages = "1374--1383",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "3",

}

TY - JOUR

T1 - Allogeneic iPSC-derived RPE cell graft failure following transplantation into the subretinal space in nonhuman primates

AU - McGill, Trevor

AU - Stoddard, Jonathan

AU - Renner, Auren M.

AU - Messaoudi, Ilhem

AU - Bharti, Kapil

AU - Mitalipov, Shoukhrat

AU - Lauer, Andreas (Andy)

AU - Wilson, David

AU - Neuringer, Martha

PY - 2018/3/1

Y1 - 2018/3/1

N2 - PURPOSE. To characterize the intraocular immune response following transplantation of iPSderived allogeneic RPE cells into the subretinal space of non–immune-suppressed rhesus macaques. METHODS. GFP-labeled allogeneic iPS-derived RPE cells were transplanted into the subretinal space of one eye (n = 6), and into the contralateral eye 1 day to 4 weeks later, using a twostage transretinal and transscleral approach. Retinas were examined pre- and post-surgery by color fundus photography, fundus autofluorescence, and optical coherence tomography (OCT) imaging. Animals were euthanized between 2 hours and 7 weeks following transplantation. T-cell (CD3), B-cell (CD20), and microglial (Iba1) responses were assessed immunohistochemically. RESULTS. Cells were delivered into the subretinal space in all eyes without leakage into the vitreous. Transplanted RPE cells were clearly visible at 4 days after surgery but were no longer detectable by 3 weeks. In localized areas within the bleb containing transplanted cells, T- and B-cell infiltrates and microglia were observed in the subretinal space and underlying choroid. A T-cell response predominated at 4 days, but converted to a B-cell response at 3 weeks. By 7 weeks, few infiltrates or microglia remained. Host RPE and choroid were disrupted in the immediate vicinity of the graft, with fibrosis in the subretinal space. CONCLUSIONS. Engraftment of allogeneic RPE cells failed following transplantation into the subretinal space of rhesus macaques, likely due to rejection by the immune system. These data underscore the need for autologous cell sources and/or confirmation of adequate immune suppression to ensure survival of transplanted RPE cells.

AB - PURPOSE. To characterize the intraocular immune response following transplantation of iPSderived allogeneic RPE cells into the subretinal space of non–immune-suppressed rhesus macaques. METHODS. GFP-labeled allogeneic iPS-derived RPE cells were transplanted into the subretinal space of one eye (n = 6), and into the contralateral eye 1 day to 4 weeks later, using a twostage transretinal and transscleral approach. Retinas were examined pre- and post-surgery by color fundus photography, fundus autofluorescence, and optical coherence tomography (OCT) imaging. Animals were euthanized between 2 hours and 7 weeks following transplantation. T-cell (CD3), B-cell (CD20), and microglial (Iba1) responses were assessed immunohistochemically. RESULTS. Cells were delivered into the subretinal space in all eyes without leakage into the vitreous. Transplanted RPE cells were clearly visible at 4 days after surgery but were no longer detectable by 3 weeks. In localized areas within the bleb containing transplanted cells, T- and B-cell infiltrates and microglia were observed in the subretinal space and underlying choroid. A T-cell response predominated at 4 days, but converted to a B-cell response at 3 weeks. By 7 weeks, few infiltrates or microglia remained. Host RPE and choroid were disrupted in the immediate vicinity of the graft, with fibrosis in the subretinal space. CONCLUSIONS. Engraftment of allogeneic RPE cells failed following transplantation into the subretinal space of rhesus macaques, likely due to rejection by the immune system. These data underscore the need for autologous cell sources and/or confirmation of adequate immune suppression to ensure survival of transplanted RPE cells.

KW - Allogeneic RPE

KW - Cell transplantation

KW - Graft failure

UR - http://www.scopus.com/inward/record.url?scp=85043569682&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85043569682&partnerID=8YFLogxK

U2 - 10.1167/iovs.17-22467

DO - 10.1167/iovs.17-22467

M3 - Article

VL - 59

SP - 1374

EP - 1383

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 3

ER -