cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates
Abstract 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 evi...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-021-02539-8 |
| _version_ | 1819066213908611072 |
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| author | Swathi Lingam Zengping Liu Binxia Yang Wendy Wong Bhav Harshad Parikh Jun Yi Ong Debbie Goh Daniel Soo Lin Wong Queenie Shu Woon Tan Gavin S. W. Tan Graham E. Holder Kakkad Regha Veluchamy Amutha Barathi Walter Hunziker Gopal Lingam Xianmin Zeng Xinyi Su |
| author_facet | Swathi Lingam Zengping Liu Binxia Yang Wendy Wong Bhav Harshad Parikh Jun Yi Ong Debbie Goh Daniel Soo Lin Wong Queenie Shu Woon Tan Gavin S. W. Tan Graham E. Holder Kakkad Regha Veluchamy Amutha Barathi Walter Hunziker Gopal Lingam Xianmin Zeng Xinyi Su |
| author_sort | Swathi Lingam |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-21T15:58:48Z |
| format | Article |
| id | doaj.art-ebb00a72f8324335bf6cabbb07433c97 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-21T15:58:48Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-ebb00a72f8324335bf6cabbb07433c972022-12-21T18:58:02ZengBMCStem Cell Research & Therapy1757-65122021-08-0112111410.1186/s13287-021-02539-8cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primatesSwathi Lingam0Zengping Liu1Binxia Yang2Wendy Wong3Bhav Harshad Parikh4Jun Yi Ong5Debbie Goh6Daniel Soo Lin Wong7Queenie Shu Woon Tan8Gavin S. W. Tan9Graham E. Holder10Kakkad Regha11Veluchamy Amutha Barathi12Walter Hunziker13Gopal Lingam14Xianmin Zeng15Xinyi Su16Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Department of Ophthalmology, National University HospitalInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Department of Ophthalmology, National University HospitalDepartment of Ophthalmology, Yong Loo Lin School of Medicine, National University of SingaporeInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Singapore Eye Research Institute (SERI)Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of SingaporeInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of SingaporeInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Physiology, Yong Loo Lin School of Medicine, National University of SingaporeInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)Abstract 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.https://doi.org/10.1186/s13287-021-02539-8Cell therapyInduced pluripotent stem cellsNon-human primatesPhotoreceptor precursors |
| spellingShingle | Swathi Lingam Zengping Liu Binxia Yang Wendy Wong Bhav Harshad Parikh Jun Yi Ong Debbie Goh Daniel Soo Lin Wong Queenie Shu Woon Tan Gavin S. W. Tan Graham E. Holder Kakkad Regha Veluchamy Amutha Barathi Walter Hunziker Gopal Lingam Xianmin Zeng Xinyi Su cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates Stem Cell Research & Therapy Cell therapy Induced pluripotent stem cells Non-human primates Photoreceptor precursors |
| 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 | Cell therapy Induced pluripotent stem cells Non-human primates Photoreceptor precursors |
| url | https://doi.org/10.1186/s13287-021-02539-8 |
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