Tags

Type your tag names separated by a space and hit enter

Allogeneic iPSC-Derived RPE Cell Graft Failure Following Transplantation Into the Subretinal Space in Nonhuman Primates.
Invest Ophthalmol Vis Sci. 2018 03 01; 59(3):1374-1383.IO

Abstract

Purpose

To characterize the intraocular immune response following transplantation of iPS-derived 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 two-stage 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.

Authors+Show Affiliations

Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States. Department of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States.Department of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States.Department of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States.Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, United States.Unit on Ocular and Stem Cell Translational Research, National Eye Institute/National Institutes of Health, Bethesda, Maryland, United States.Department of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States.Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States. Department of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29625461

Citation

McGill, Trevor J., et al. "Allogeneic iPSC-Derived RPE Cell Graft Failure Following Transplantation Into the Subretinal Space in Nonhuman Primates." Investigative Ophthalmology & Visual Science, vol. 59, no. 3, 2018, pp. 1374-1383.
McGill TJ, Stoddard J, Renner LM, et al. Allogeneic iPSC-Derived RPE Cell Graft Failure Following Transplantation Into the Subretinal Space in Nonhuman Primates. Invest Ophthalmol Vis Sci. 2018;59(3):1374-1383.
McGill, T. J., Stoddard, J., Renner, L. M., Messaoudi, I., Bharti, K., Mitalipov, S., Lauer, A., Wilson, D. J., & Neuringer, M. (2018). Allogeneic iPSC-Derived RPE Cell Graft Failure Following Transplantation Into the Subretinal Space in Nonhuman Primates. Investigative Ophthalmology & Visual Science, 59(3), 1374-1383. https://doi.org/10.1167/iovs.17-22467
McGill TJ, et al. Allogeneic iPSC-Derived RPE Cell Graft Failure Following Transplantation Into the Subretinal Space in Nonhuman Primates. Invest Ophthalmol Vis Sci. 2018 03 1;59(3):1374-1383. PubMed PMID: 29625461.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Allogeneic iPSC-Derived RPE Cell Graft Failure Following Transplantation Into the Subretinal Space in Nonhuman Primates. AU - McGill,Trevor J, AU - Stoddard,Jonathan, AU - Renner,Lauren M, AU - Messaoudi,Ilhem, AU - Bharti,Kapil, AU - Mitalipov,Shoukhrat, AU - Lauer,Andreas, AU - Wilson,David J, AU - Neuringer,Martha, PY - 2018/4/7/entrez PY - 2018/4/7/pubmed PY - 2018/8/22/medline SP - 1374 EP - 1383 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 59 IS - 3 N2 - Purpose: To characterize the intraocular immune response following transplantation of iPS-derived 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 two-stage 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. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/29625461/Allogeneic_iPSC_Derived_RPE_Cell_Graft_Failure_Following_Transplantation_Into_the_Subretinal_Space_in_Nonhuman_Primates_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.17-22467 DB - PRIME DP - Unbound Medicine ER -