Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats

Retinal pigment epithelium (RPE) replacement therapy is evolving as a feasible approach to treat age-related macular degeneration (AMD). In many preclinical studies, RPE cells are transplanted as a cell suspension into immunosuppressed animal eyes and transplant effects have been monitored only shor...

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Autores principales:	Deepthi S. Rajendran Nair, Danhong Zhu, Ruchi Sharma, Juan Carlos Martinez Camarillo, Kapil Bharti, David R. Hinton, Mark S. Humayun, Biju B. Thomas
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	iPSC-RPE retinal pigment epithelium immunodeficient RCS rat ultrathin parylene retinal degeneration retinal transplantation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0be3be12448847bb9cacd7559b8922c4
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spelling	oai:doaj.org-article:0be3be12448847bb9cacd7559b8922c42021-11-25T17:09:44ZLong-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats10.3390/cells101129512073-4409https://doaj.org/article/0be3be12448847bb9cacd7559b8922c42021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2951https://doaj.org/toc/2073-4409Retinal pigment epithelium (RPE) replacement therapy is evolving as a feasible approach to treat age-related macular degeneration (AMD). In many preclinical studies, RPE cells are transplanted as a cell suspension into immunosuppressed animal eyes and transplant effects have been monitored only short-term. We investigated the long-term effects of human Induced pluripotent stem-cell-derived RPE (iPSC-RPE) transplants in an immunodeficient Royal College of Surgeons (RCS) rat model, in which RPE dysfunction led to photoreceptor degeneration. iPSC-RPE cultured as a polarized monolayer on a nanoengineered ultrathin parylene C scaffold was transplanted into the subretinal space of 28-day-old immunodeficient RCS rat pups and evaluated after 1, 4, and 11 months. Assessment at early time points showed good iPSC-RPE survival. The transplants remained as a monolayer, expressed RPE-specific markers, performed phagocytic function, and contributed to vision preservation. At 11-months post-implantation, RPE survival was observed in only 50% of the eyes that were concomitant with vision preservation. Loss of RPE monolayer characteristics at the 11-month time point was associated with peri-membrane fibrosis, immune reaction through the activation of macrophages (CD 68 expression), and the transition of cell fate (expression of mesenchymal markers). The overall study outcome supports the therapeutic potential of RPE grafts despite the loss of some transplant benefits during long-term observations.Deepthi S. Rajendran NairDanhong ZhuRuchi SharmaJuan Carlos Martinez CamarilloKapil BhartiDavid R. HintonMark S. HumayunBiju B. ThomasMDPI AGarticleiPSC-RPEretinal pigment epitheliumimmunodeficient RCS ratultrathin paryleneretinal degenerationretinal transplantationBiology (General)QH301-705.5ENCells, Vol 10, Iss 2951, p 2951 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	iPSC-RPE retinal pigment epithelium immunodeficient RCS rat ultrathin parylene retinal degeneration retinal transplantation Biology (General) QH301-705.5
spellingShingle	iPSC-RPE retinal pigment epithelium immunodeficient RCS rat ultrathin parylene retinal degeneration retinal transplantation Biology (General) QH301-705.5 Deepthi S. Rajendran Nair Danhong Zhu Ruchi Sharma Juan Carlos Martinez Camarillo Kapil Bharti David R. Hinton Mark S. Humayun Biju B. Thomas Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats
description	Retinal pigment epithelium (RPE) replacement therapy is evolving as a feasible approach to treat age-related macular degeneration (AMD). In many preclinical studies, RPE cells are transplanted as a cell suspension into immunosuppressed animal eyes and transplant effects have been monitored only short-term. We investigated the long-term effects of human Induced pluripotent stem-cell-derived RPE (iPSC-RPE) transplants in an immunodeficient Royal College of Surgeons (RCS) rat model, in which RPE dysfunction led to photoreceptor degeneration. iPSC-RPE cultured as a polarized monolayer on a nanoengineered ultrathin parylene C scaffold was transplanted into the subretinal space of 28-day-old immunodeficient RCS rat pups and evaluated after 1, 4, and 11 months. Assessment at early time points showed good iPSC-RPE survival. The transplants remained as a monolayer, expressed RPE-specific markers, performed phagocytic function, and contributed to vision preservation. At 11-months post-implantation, RPE survival was observed in only 50% of the eyes that were concomitant with vision preservation. Loss of RPE monolayer characteristics at the 11-month time point was associated with peri-membrane fibrosis, immune reaction through the activation of macrophages (CD 68 expression), and the transition of cell fate (expression of mesenchymal markers). The overall study outcome supports the therapeutic potential of RPE grafts despite the loss of some transplant benefits during long-term observations.
format	article
author	Deepthi S. Rajendran Nair Danhong Zhu Ruchi Sharma Juan Carlos Martinez Camarillo Kapil Bharti David R. Hinton Mark S. Humayun Biju B. Thomas
author_facet	Deepthi S. Rajendran Nair Danhong Zhu Ruchi Sharma Juan Carlos Martinez Camarillo Kapil Bharti David R. Hinton Mark S. Humayun Biju B. Thomas
author_sort	Deepthi S. Rajendran Nair
title	Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats
title_short	Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats
title_full	Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats
title_fullStr	Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats
title_full_unstemmed	Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats
title_sort	long-term transplant effects of ipsc-rpe monolayer in immunodeficient rcs rats
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0be3be12448847bb9cacd7559b8922c4
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Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats

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