iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study
Phototransduction is accomplished in the retina by photoreceptor neurons and retinal pigment epithelium (RPE) cells. Photoreceptors rely heavily on the RPE, and death or dysfunction of RPE is characteristic of age-related macular degeneration (AMD), a very common neurodegenerative disease for which...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/8470263 |
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| author | Peter D. Westenskow Felicitas Bucher Stephen Bravo Toshihide Kurihara Daniel Feitelberg Liliana P. Paris Edith Aguilar Jonathan H. Lin Martin Friedlander |
| author_facet | Peter D. Westenskow Felicitas Bucher Stephen Bravo Toshihide Kurihara Daniel Feitelberg Liliana P. Paris Edith Aguilar Jonathan H. Lin Martin Friedlander |
| author_sort | Peter D. Westenskow |
| collection | DOAJ |
| description | Phototransduction is accomplished in the retina by photoreceptor neurons and retinal pigment epithelium (RPE) cells. Photoreceptors rely heavily on the RPE, and death or dysfunction of RPE is characteristic of age-related macular degeneration (AMD), a very common neurodegenerative disease for which no cure exists. RPE replacement is a promising therapeutic intervention for AMD, and large numbers of RPE cells can be generated from pluripotent stem cells. However, questions persist regarding iPSC-derived RPE (iPS-RPE) viability, immunogenicity, and tumorigenesis potential. We showed previously that iPS-RPE prevent photoreceptor atrophy in dystrophic rats up until 24 weeks after implantation. In this follow-up study, we longitudinally monitored the same implanted iPS-RPE, in the same animals. We observed no gross abnormalities in the eyes, livers, spleens, brains, and blood in aging rats with iPSC-RPE grafts. iPS-RPE cells that integrated into the subretinal space outlived the photoreceptors and survived for as long as 2 1/2 years while nonintegrating RPE cells were ingested by host macrophages. Both populations could be distinguished using immunohistochemistry and electron microscopy. iPSC-RPE could be isolated from the grafts and maintained in culture; these cells also phagocytosed isolated photoreceptor outer segments. We conclude that iPS-RPE grafts remain viable and do not induce any obvious associated pathological changes. |
| format | Article |
| id | doaj-art-a55cb2c49e18461a8fc991a4c2774f1c |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-a55cb2c49e18461a8fc991a4c2774f1c2025-02-03T01:03:21ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/84702638470263iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up StudyPeter D. Westenskow0Felicitas Bucher1Stephen Bravo2Toshihide Kurihara3Daniel Feitelberg4Liliana P. Paris5Edith Aguilar6Jonathan H. Lin7Martin Friedlander8Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Pathology, VA San Diego Healthcare System, University of California San Diego, La Jolla, CA 92037, USADepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USAPhototransduction is accomplished in the retina by photoreceptor neurons and retinal pigment epithelium (RPE) cells. Photoreceptors rely heavily on the RPE, and death or dysfunction of RPE is characteristic of age-related macular degeneration (AMD), a very common neurodegenerative disease for which no cure exists. RPE replacement is a promising therapeutic intervention for AMD, and large numbers of RPE cells can be generated from pluripotent stem cells. However, questions persist regarding iPSC-derived RPE (iPS-RPE) viability, immunogenicity, and tumorigenesis potential. We showed previously that iPS-RPE prevent photoreceptor atrophy in dystrophic rats up until 24 weeks after implantation. In this follow-up study, we longitudinally monitored the same implanted iPS-RPE, in the same animals. We observed no gross abnormalities in the eyes, livers, spleens, brains, and blood in aging rats with iPSC-RPE grafts. iPS-RPE cells that integrated into the subretinal space outlived the photoreceptors and survived for as long as 2 1/2 years while nonintegrating RPE cells were ingested by host macrophages. Both populations could be distinguished using immunohistochemistry and electron microscopy. iPSC-RPE could be isolated from the grafts and maintained in culture; these cells also phagocytosed isolated photoreceptor outer segments. We conclude that iPS-RPE grafts remain viable and do not induce any obvious associated pathological changes.http://dx.doi.org/10.1155/2016/8470263 |
| spellingShingle | Peter D. Westenskow Felicitas Bucher Stephen Bravo Toshihide Kurihara Daniel Feitelberg Liliana P. Paris Edith Aguilar Jonathan H. Lin Martin Friedlander iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study Stem Cells International |
| title | iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study |
| title_full | iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study |
| title_fullStr | iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study |
| title_full_unstemmed | iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study |
| title_short | iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study |
| title_sort | ipsc derived retinal pigment epithelium allografts do not elicit detrimental effects in rats a follow up study |
| url | http://dx.doi.org/10.1155/2016/8470263 |
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