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Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients

BACKGROUND: Retinitis pigmentosa is a common genetic disease that causes retinal degeneration and blindness for which there is currently no curable treatment available. Vision preservation was observed in retinitis pigmentosa animal models after retinal stem cell transplantation. However, long-term...

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Autores principales: Liu, Yong, Chen, Shao Jun, Li, Shi Ying, Qu, Ling Hui, Meng, Xiao Hong, Wang, Yi, Xu, Hai Wei, Liang, Zhi Qing, Yin, Zheng Qin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622579/
https://www.ncbi.nlm.nih.gov/pubmed/28962643
http://dx.doi.org/10.1186/s13287-017-0661-8
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author Liu, Yong
Chen, Shao Jun
Li, Shi Ying
Qu, Ling Hui
Meng, Xiao Hong
Wang, Yi
Xu, Hai Wei
Liang, Zhi Qing
Yin, Zheng Qin
author_facet Liu, Yong
Chen, Shao Jun
Li, Shi Ying
Qu, Ling Hui
Meng, Xiao Hong
Wang, Yi
Xu, Hai Wei
Liang, Zhi Qing
Yin, Zheng Qin
author_sort Liu, Yong
collection PubMed
description BACKGROUND: Retinitis pigmentosa is a common genetic disease that causes retinal degeneration and blindness for which there is currently no curable treatment available. Vision preservation was observed in retinitis pigmentosa animal models after retinal stem cell transplantation. However, long-term safety studies and visual assessment have not been thoroughly tested in retinitis pigmentosa patients. METHODS: In our pre-clinical study, purified human fetal-derived retinal progenitor cells (RPCs) were transplanted into the diseased retina of Royal College of Surgeons (RCS) rats, a model of retinal degeneration. Based on these results, we conducted a phase I clinical trial to establish the safety and tolerability of transplantation of RPCs in eight patients with advanced retinitis pigmentosa. Patients were studied for 24 months. RESULTS: After RPC transplantation in RCS rats, we observed moderate recovery of vision and maintenance of the outer nuclear layer thickness. Most importantly, we did not find tumor formation or immune rejection. In the retinis pigmentosa patients given RPC injections, we also did not observe immunological rejection or tumorigenesis when immunosuppressive agents were not administered. We observed a significant improvement in visual acuity (P < 0.05) in five patients and an increase in retinal sensitivity of pupillary responses in three of the eight patients between 2 and 6 months after the transplant, but this improvement did not appear by 12 months. CONCLUSION: Our study for the first time confirmed the long-term safety and feasibility of vision repair by stem cell therapy in patients blinded by retinitis pigmentosa. TRIAL REGISTRATION: WHO Trial Registration, ChiCTR-TNRC-08000193. Retrospectively registered on 5 December 2008. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-017-0661-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-56225792017-10-12 Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients Liu, Yong Chen, Shao Jun Li, Shi Ying Qu, Ling Hui Meng, Xiao Hong Wang, Yi Xu, Hai Wei Liang, Zhi Qing Yin, Zheng Qin Stem Cell Res Ther Research BACKGROUND: Retinitis pigmentosa is a common genetic disease that causes retinal degeneration and blindness for which there is currently no curable treatment available. Vision preservation was observed in retinitis pigmentosa animal models after retinal stem cell transplantation. However, long-term safety studies and visual assessment have not been thoroughly tested in retinitis pigmentosa patients. METHODS: In our pre-clinical study, purified human fetal-derived retinal progenitor cells (RPCs) were transplanted into the diseased retina of Royal College of Surgeons (RCS) rats, a model of retinal degeneration. Based on these results, we conducted a phase I clinical trial to establish the safety and tolerability of transplantation of RPCs in eight patients with advanced retinitis pigmentosa. Patients were studied for 24 months. RESULTS: After RPC transplantation in RCS rats, we observed moderate recovery of vision and maintenance of the outer nuclear layer thickness. Most importantly, we did not find tumor formation or immune rejection. In the retinis pigmentosa patients given RPC injections, we also did not observe immunological rejection or tumorigenesis when immunosuppressive agents were not administered. We observed a significant improvement in visual acuity (P < 0.05) in five patients and an increase in retinal sensitivity of pupillary responses in three of the eight patients between 2 and 6 months after the transplant, but this improvement did not appear by 12 months. CONCLUSION: Our study for the first time confirmed the long-term safety and feasibility of vision repair by stem cell therapy in patients blinded by retinitis pigmentosa. TRIAL REGISTRATION: WHO Trial Registration, ChiCTR-TNRC-08000193. Retrospectively registered on 5 December 2008. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-017-0661-8) contains supplementary material, which is available to authorized users. BioMed Central 2017-09-29 /pmc/articles/PMC5622579/ /pubmed/28962643 http://dx.doi.org/10.1186/s13287-017-0661-8 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Liu, Yong
Chen, Shao Jun
Li, Shi Ying
Qu, Ling Hui
Meng, Xiao Hong
Wang, Yi
Xu, Hai Wei
Liang, Zhi Qing
Yin, Zheng Qin
Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients
title Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients
title_full Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients
title_fullStr Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients
title_full_unstemmed Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients
title_short Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients
title_sort long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622579/
https://www.ncbi.nlm.nih.gov/pubmed/28962643
http://dx.doi.org/10.1186/s13287-017-0661-8
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