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Allogenic iPSC-derived RPE cell transplants induce immune response in pigs: a pilot study.
Sci Rep. 2015 Jul 03; 5:11791.SR

Abstract

Stem cell strategies focused on replacement of RPE cells for the treatment of geographic atrophy are under intense investigation. Although the eye has long been considered immune privileged, there is limited information about the immune response to transplanted cells in the subretinal space of large animals. The purpose of this study was to evaluate the survival of allogenic induced pluripotent stem cell-derived RPE cells (iPSC-RPE) delivered to the subretinal space of the pig as well as determine whether these cells induce an immune response in non-diseased eyes. GFP positive iPSC-RPE, generated from outbred domestic swine, were injected into the subretinal space of vitrectomized miniature swine. Control eyes received vehicle only. GFP positive iPSC-RPE cells were identified in the subretinal space 3 weeks after injection in 5 of 6 eyes. Accompanying GFP-negative cells positive for IgG, CD45 and macrophage markers were also identified in close proximity to the injected iPSC-RPE cells. All subretinal cells were negative for GFAP as well as cell cycle markers. We found that subretinal injection of allogenic iPSC-RPE cells into wild-type mini-pigs can induce the innate immune response. These findings suggest that immunologically matched or autologous donor cells should be considered for clinical RPE cell replacement.

Authors+Show Affiliations

Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA.Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA.Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA.Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA.Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA.Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA.Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA.

Pub Type(s)

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

Language

eng

PubMed ID

26138532

Citation

Sohn, Elliott H., et al. "Allogenic iPSC-derived RPE Cell Transplants Induce Immune Response in Pigs: a Pilot Study." Scientific Reports, vol. 5, 2015, p. 11791.
Sohn EH, Jiao C, Kaalberg E, et al. Allogenic iPSC-derived RPE cell transplants induce immune response in pigs: a pilot study. Sci Rep. 2015;5:11791.
Sohn, E. H., Jiao, C., Kaalberg, E., Cranston, C., Mullins, R. F., Stone, E. M., & Tucker, B. A. (2015). Allogenic iPSC-derived RPE cell transplants induce immune response in pigs: a pilot study. Scientific Reports, 5, 11791. https://doi.org/10.1038/srep11791
Sohn EH, et al. Allogenic iPSC-derived RPE Cell Transplants Induce Immune Response in Pigs: a Pilot Study. Sci Rep. 2015 Jul 3;5:11791. PubMed PMID: 26138532.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Allogenic iPSC-derived RPE cell transplants induce immune response in pigs: a pilot study. AU - Sohn,Elliott H, AU - Jiao,Chunhua, AU - Kaalberg,Emily, AU - Cranston,Cathryn, AU - Mullins,Robert F, AU - Stone,Edwin M, AU - Tucker,Budd A, Y1 - 2015/07/03/ PY - 2014/10/03/received PY - 2015/06/05/accepted PY - 2015/7/4/entrez PY - 2015/7/4/pubmed PY - 2016/8/2/medline SP - 11791 EP - 11791 JF - Scientific reports JO - Sci Rep VL - 5 N2 - Stem cell strategies focused on replacement of RPE cells for the treatment of geographic atrophy are under intense investigation. Although the eye has long been considered immune privileged, there is limited information about the immune response to transplanted cells in the subretinal space of large animals. The purpose of this study was to evaluate the survival of allogenic induced pluripotent stem cell-derived RPE cells (iPSC-RPE) delivered to the subretinal space of the pig as well as determine whether these cells induce an immune response in non-diseased eyes. GFP positive iPSC-RPE, generated from outbred domestic swine, were injected into the subretinal space of vitrectomized miniature swine. Control eyes received vehicle only. GFP positive iPSC-RPE cells were identified in the subretinal space 3 weeks after injection in 5 of 6 eyes. Accompanying GFP-negative cells positive for IgG, CD45 and macrophage markers were also identified in close proximity to the injected iPSC-RPE cells. All subretinal cells were negative for GFAP as well as cell cycle markers. We found that subretinal injection of allogenic iPSC-RPE cells into wild-type mini-pigs can induce the innate immune response. These findings suggest that immunologically matched or autologous donor cells should be considered for clinical RPE cell replacement. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/26138532/Allogenic_iPSC_derived_RPE_cell_transplants_induce_immune_response_in_pigs:_a_pilot_study_ L2 - https://doi.org/10.1038/srep11791 DB - PRIME DP - Unbound Medicine ER -