Establishment of Immunodeficient Retinal Degeneration Model Mice and Functional Maturation of Human ESC-Derived Retinal Sheets after Transplantation

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Author(s)

    • 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
    • Tu Hung-Ya
    • Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
    • Yamasaki Suguru
    • Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN・Regenerative and Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd.
    • Kagawa Takahiro
    • Central Institute for Experimental Animals, Animal Resources and Technical Research Center
    • Goto Motohito
    • Central Institute for Experimental Animals, Animal Resources and Technical Research Center
    • Takahashi Riichi
    • Central Institute for Experimental Animals, Animal Resources and Technical Research Center
    • Watanabe Takehito
    • Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
    • Sugita Sunao
    • Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
    • Yonemura Shigenobu
    • Ultrastructural Research Team, RIKEN Center for Life Science Technologies.・Department of Cell Biology, Tokushima University Graduate School of Medical Science
    • Matsuyama Take
    • Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
    • Fujii Momo
    • Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
    • Kuwahara Atsushi
    • Regenerative and Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd.
    • Kishino Akiyoshi
    • Regenerative and Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd.
    • Koide Naoshi
    • Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN
    • Eiraku Mototsugu
    • Laboratory for in vitro Histogenesis, RIKEN Center for Developmental Biology
    • Takahashi Masayo
    • Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN・Application Biology and Regenerative Medicine, Graduate School of Medicine, Kyoto University
    • 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

  • Stem Cell Reports

    Stem Cell Reports (10), 1059-1074, 2018-03-13

    Elsevier BV

Codes

  • NII Article ID (NAID)
    120006425880
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    2213-6711
  • Data Source
    IR 
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