Establishment of Immunodeficient Retinal Degeneration Model Mice and Functional Maturation of Human ESC-Derived Retinal Sheets after Transplantation
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- Iraha Satoshi
- Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN・Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University・Application Biology and Regenerative Medicine, Graduate School of Medicine, Kyoto University
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- Tu Hung-Ya
- Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
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- Yamasaki Suguru
- Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN・Regenerative and Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd.
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- Kagawa Takahiro
- Central Institute for Experimental Animals, Animal Resources and Technical Research Center
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- Goto Motohito
- Central Institute for Experimental Animals, Animal Resources and Technical Research Center
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- Takahashi Riichi
- Central Institute for Experimental Animals, Animal Resources and Technical Research Center
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- Watanabe Takehito
- Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
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- Sugita Sunao
- Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
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- Yonemura Shigenobu
- Ultrastructural Research Team, RIKEN Center for Life Science Technologies.・Department of Cell Biology, Tokushima University Graduate School of Medical Science
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- Sunagawa Genshiro A.
- Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
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- Matsuyama Take
- Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
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- Fujii Momo
- Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
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- Kuwahara Atsushi
- Regenerative and Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd.
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- Kishino Akiyoshi
- Regenerative and Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd.
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- Koide Naoshi
- Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
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- Eiraku Mototsugu
- Laboratory for in vitro Histogenesis, RIKEN Center for Developmental Biology
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- Tanihara Hidenobu
- Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University
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- Takahashi Masayo
- Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN・Application Biology and Regenerative Medicine, Graduate School of Medicine, Kyoto University
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- Mandai Michiko
- Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN・RIKEN Program for Drug Discovery and Medical Technology Platforms (DMP)
Abstract
Increasing demand for clinical retinal degeneration therapies featuring human ESC/iPSC-derived retinal tissue and cells warrants proof-of-concept studies. Here, we established two mouse models of end-stage retinal degeneration with immunodeficiency, NOG-rd1-2J and NOG-rd10, and characterized disease progress and immunodeficient status. We also transplanted human ESC-derived retinal sheets into NOG-rd1-2J and confirmed their long-term survival and maturation of the structured graft photoreceptor layer, without rejection or tumorigenesis. We recorded light responses from the host ganglion cells using a multi-electrode array system; this result was consistent with whole-mount immunostaining suggestive of host-graft synapse formation at the responding sites. This study demonstrates an application of our mouse models and provides a proof of concept for the clinical use of human ESC-derived retinal sheets.
Journal
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- Stem Cell Reports
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Stem Cell Reports (10), 1059-1074, 2018-03-13
Elsevier BV