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

Stem Cell Reports. 2018 Mar 13;10(3):1059-1074. doi: 10.1016/j.stemcr.2018.01.032. Epub 2018 Mar 1.


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.

Keywords: human ESC; multiple electrode array; photoreceptor transplantation; retinal degeneration; retinal regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Embryonic Stem Cells / pathology*
  • Female
  • Humans
  • Induced Pluripotent Stem Cells / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Photoreceptor Cells / pathology
  • Retina / pathology*
  • Retinal Degeneration / pathology*
  • Stem Cell Transplantation / methods