Allogenic iPSC-derived RPE cell transplants induce immune response in pigs: a pilot study

Elliott H Sohn; Chunhua Jiao; Emily Kaalberg; Cathryn Cranston; Robert F Mullins; Edwin M Stone; Budd A Tucker

doi:10.1038/srep11791

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Allogenic iPSC-derived RPE cell transplants induce immune response in pigs: a pilot study

Journal article

Open access

Peer reviewed

Allogenic iPSC-derived RPE cell transplants induce immune response in pigs: a pilot study

Elliott H Sohn, Chunhua Jiao, Emily Kaalberg, Cathryn Cranston, Robert F Mullins, Edwin M Stone and Budd A Tucker

Scientific reports, Vol.5(1), pp.11791-11791

07/03/2015

DOI: 10.1038/srep11791

PMCID: PMC4490339

PMID: 26138532

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https://doi.org/10.1038/srep11791View

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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.

Eye - pathology

Retinal Pigment Epithelium - transplantation

Humans

Induced Pluripotent Stem Cells - transplantation

Immunity, Innate

Stem Cell Transplantation

Retinal Pigment Epithelium - pathology

Pilot Projects

Animals

Swine

Swine, Miniature

Eye - transplantation

Retina - pathology

Details

Title: Subtitle: Allogenic iPSC-derived RPE cell transplants induce immune response in pigs: a pilot study
Creators: Elliott H Sohn - Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA
Chunhua Jiao - Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA
Emily Kaalberg - Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA
Cathryn Cranston - Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA
Robert F Mullins - Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA
Edwin M Stone - Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA
Budd A Tucker - Stephen A Wynn Institute for Vision Research, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA
Resource Type: Journal article
Publication Details: Scientific reports, Vol.5(1), pp.11791-11791
DOI: 10.1038/srep11791
PMID: 26138532
PMCID: PMC4490339
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: R01 EY024605 / NEI NIH HHS EY-024605 / NEI NIH HHS R01 EY016822 / NEI NIH HHS DP2 OD007483 / NIH HHS Howard Hughes Medical Institute EY-016822 / NEI NIH HHS 1DP2OD007483 / NIH HHS
Language: English
Date published: 07/03/2015
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983980052402771

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