iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up StudyReportar como inadecuado




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Stem Cells International - Volume 2016 2016, Article ID 8470263, 8 pages -

Research Article

Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA

The Lowy Medical Research Institute, La Jolla, CA 92037, USA

Department of Pathology, VA San Diego Healthcare System, University of California San Diego, La Jolla, CA 92037, USA

Received 14 July 2015; Accepted 20 October 2015

Academic Editor: William L. Stanford

Copyright © 2016 Peter D. Westenskow et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.





Autor: Peter D. Westenskow, Felicitas Bucher, Stephen Bravo, Toshihide Kurihara, Daniel Feitelberg, Liliana P. Paris, Edith Aguilar

Fuente: https://www.hindawi.com/



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