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

被引：86

作者：

Iraha, Satoshi ^{[1
,2
,3
]}

Tu, Hung-Ya ^{[1
]}

Yamasaki, Suguru ^{[1
,4
]}

Kagawa, Takahiro ^{[5
]}

Goto, Motohito ^{[5
]}

Takahashi, Riichi ^{[5
]}

Watanabe, Takehito ^{[1
]}

Sugita, Sunao ^{[1
]}

Yonemura, Shigenobu ^{[6
,7
]}

Sunagawa, Genshiro A. ^{[1
]}

Matsuyama, Take ^{[1
]}

Fujii, Momo ^{[1
]}

Kuwahara, Atsushi ^{[4
]}

Kishino, Akiyoshi ^{[4
]}

Koide, Naoshi ^{[1
]}

Eiraku, Mototsugu ^{[8
]}

Tanihara, Hidenobu ^{[2
]}

Takahashi, Masayo ^{[1
,3
]}

Mandai, Michiko ^{[1
,9
]}

机构：

[1] RIKEN, Ctr Dev Biol, Lab Retinal Regenerat, Kobe, Hyogo 6500047, Japan

[2] Kumamoto Univ, Fac Life Sci, Dept Ophthalmol, Kumamoto 8608556, Japan

[3] Kyoto Univ, Grad Sch Med, Applicat Biol & Regenerat Med, Kyoto 6068501, Japan

[4] Sumitomo Dainippon Pharma Co Ltd, Regenerat & Cellular Med Off, Kobe, Hyogo 6500047, Japan

[5] Anim Resources & Tech Res Ctr, Cent Inst Expt Anim, Kawasaki, Kanagawa 2100821, Japan

[6] RIKEN, Ctr Life Sci Technol, Ultrastruct Res Team, Kobe, Hyogo 6500047, Japan

[7] Tokushima Univ, Grad Sch Med Sci, Dept Cell Biol, Tokushima 7708503, Japan

[8] RIKEN, Ctr Dev Biol, Lab Vitro Histogenesis, Kobe, Hyogo 6500047, Japan

[9] RIKEN, Program Drug Discovery & Med Technol Platforms DM, Kobe, Hyogo 6500047, Japan

来源：

STEM CELL REPORTS | 2018年 / 10卷 / 03期

关键词：

CHRONIC INFLAMMATORY REACTION; MOUSE MODEL; MICROGLIAL PHAGOCYTOSIS; HOST PHOTORECEPTORS; ACTIVATION; INTEGRATE; RESPONSES; PROTEINS; VISION; TISSUE;

D O I：

10.1016/j.stemcr.2018.01.032

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：1059 / 1074

页数：16

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