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cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates
BACKGROUND: Retinal regenerative therapies hold great promise for the treatment of inherited retinal degenerations (IRDs). Studies in preclinical lower mammal models of IRDs have suggested visual improvement following retinal photoreceptor precursors transplantation, but there is limited evidence on...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375124/ https://www.ncbi.nlm.nih.gov/pubmed/34412697 http://dx.doi.org/10.1186/s13287-021-02539-8 |
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author | Lingam, Swathi Liu, Zengping Yang, Binxia Wong, Wendy Parikh, Bhav Harshad Ong, Jun Yi Goh, Debbie Wong, Daniel Soo Lin Tan, Queenie Shu Woon Tan, Gavin S. W. Holder, Graham E. Regha, Kakkad Barathi, Veluchamy Amutha Hunziker, Walter Lingam, Gopal Zeng, Xianmin Su, Xinyi |
author_facet | Lingam, Swathi Liu, Zengping Yang, Binxia Wong, Wendy Parikh, Bhav Harshad Ong, Jun Yi Goh, Debbie Wong, Daniel Soo Lin Tan, Queenie Shu Woon Tan, Gavin S. W. Holder, Graham E. Regha, Kakkad Barathi, Veluchamy Amutha Hunziker, Walter Lingam, Gopal Zeng, Xianmin Su, Xinyi |
author_sort | Lingam, Swathi |
collection | PubMed |
description | BACKGROUND: Retinal regenerative therapies hold great promise for the treatment of inherited retinal degenerations (IRDs). Studies in preclinical lower mammal models of IRDs have suggested visual improvement following retinal photoreceptor precursors transplantation, but there is limited evidence on the ability of these transplants to rescue retinal damage in higher mammals. The purpose of this study was to evaluate the therapeutic potential of photoreceptor precursors derived from clinically compliant induced pluripotent stem cells (iPSCs). METHODS: Photoreceptor precursors were sub-retinally transplanted into non-human primates (Macaca fascicularis). The cells were transplanted both in naïve and cobalt chloride-induced retinal degeneration models who had been receiving systemic immunosuppression for one week prior to the procedure. Optical coherence tomography, fundus autofluorescence imaging, electroretinography, ex vivo histology and immunofluorescence staining were used to evaluate retinal structure, function and survival of transplanted cells. RESULTS: There were no adverse effects of iPSC-derived photoreceptor precursors on retinal structure or function in naïve NHP models, indicating good biocompatibility. In addition, photoreceptor precursors injected into cobalt chloride-induced retinal degeneration NHP models demonstrated an ability both to survive and to mature into cone photoreceptors at 3 months post-transplant. Optical coherence tomography showed restoration of retinal ellipsoid zone post-transplantation. CONCLUSIONS: These findings demonstrate the safety and therapeutic potential of clinically compliant iPSC-derived photoreceptor precursors as a cell replacement source for future clinical trials. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02539-8. |
format | Online Article Text |
id | pubmed-8375124 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-83751242021-08-19 cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates Lingam, Swathi Liu, Zengping Yang, Binxia Wong, Wendy Parikh, Bhav Harshad Ong, Jun Yi Goh, Debbie Wong, Daniel Soo Lin Tan, Queenie Shu Woon Tan, Gavin S. W. Holder, Graham E. Regha, Kakkad Barathi, Veluchamy Amutha Hunziker, Walter Lingam, Gopal Zeng, Xianmin Su, Xinyi Stem Cell Res Ther Research BACKGROUND: Retinal regenerative therapies hold great promise for the treatment of inherited retinal degenerations (IRDs). Studies in preclinical lower mammal models of IRDs have suggested visual improvement following retinal photoreceptor precursors transplantation, but there is limited evidence on the ability of these transplants to rescue retinal damage in higher mammals. The purpose of this study was to evaluate the therapeutic potential of photoreceptor precursors derived from clinically compliant induced pluripotent stem cells (iPSCs). METHODS: Photoreceptor precursors were sub-retinally transplanted into non-human primates (Macaca fascicularis). The cells were transplanted both in naïve and cobalt chloride-induced retinal degeneration models who had been receiving systemic immunosuppression for one week prior to the procedure. Optical coherence tomography, fundus autofluorescence imaging, electroretinography, ex vivo histology and immunofluorescence staining were used to evaluate retinal structure, function and survival of transplanted cells. RESULTS: There were no adverse effects of iPSC-derived photoreceptor precursors on retinal structure or function in naïve NHP models, indicating good biocompatibility. In addition, photoreceptor precursors injected into cobalt chloride-induced retinal degeneration NHP models demonstrated an ability both to survive and to mature into cone photoreceptors at 3 months post-transplant. Optical coherence tomography showed restoration of retinal ellipsoid zone post-transplantation. CONCLUSIONS: These findings demonstrate the safety and therapeutic potential of clinically compliant iPSC-derived photoreceptor precursors as a cell replacement source for future clinical trials. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02539-8. BioMed Central 2021-08-19 /pmc/articles/PMC8375124/ /pubmed/34412697 http://dx.doi.org/10.1186/s13287-021-02539-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Lingam, Swathi Liu, Zengping Yang, Binxia Wong, Wendy Parikh, Bhav Harshad Ong, Jun Yi Goh, Debbie Wong, Daniel Soo Lin Tan, Queenie Shu Woon Tan, Gavin S. W. Holder, Graham E. Regha, Kakkad Barathi, Veluchamy Amutha Hunziker, Walter Lingam, Gopal Zeng, Xianmin Su, Xinyi cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates |
title | cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates |
title_full | cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates |
title_fullStr | cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates |
title_full_unstemmed | cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates |
title_short | cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates |
title_sort | cgmp-grade human ipsc-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375124/ https://www.ncbi.nlm.nih.gov/pubmed/34412697 http://dx.doi.org/10.1186/s13287-021-02539-8 |
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