Establishment of Immunodeficient Retinal Degeneration Model Mice and Functional Maturation of Human ESC-Derived Retinal Sheets after Transplantation.
Establishment of Immunodeficient Retinal Degeneration Model Mice and Functional Maturation of Human ESC-Derived Retinal Sheets after Transplantation.
复制标题
DOI：
10.1016/j.stemcr.2018.01.032
复制
发表时间：
2018-03-13
影响因子：
5.9
通讯作者：
Mandai M
中科院分区：
文献类型：
--
作者：
Iraha S;Tu HY;Yamasaki S;Kagawa T;Goto M;Takahashi R;Watanabe T;Sugita S;Yonemura S;Sunagawa GA;Matsuyama T;Fujii M;Kuwahara A;Kishino A;Koide N;Eiraku M;Tanihara H;Takahashi M;Mandai M
对以人ESC/iPSC衍生的视网膜组织和细胞为特征的临床视网膜变性治疗的需求日益增加，这需要进行概念验证研究。在这里，我们建立了两个终末期视网膜变性与免疫缺陷，NOG-rd 1 - 2 J和NOG-rd 10小鼠模型，并表征疾病进展和免疫缺陷状态。我们还将人ESC衍生的视网膜片移植到NOG-rd 1 - 2 J中，并证实了它们的长期存活和结构化移植感光层的成熟，而没有排斥反应或肿瘤发生。我们使用多电极阵列系统记录了宿主神经节细胞的光反应;这一结果与提示在反应位点形成宿主-移植物突触的整装免疫染色一致。本研究证明了我们的小鼠模型的应用，并为人类ESC衍生的视网膜片的临床应用提供了概念证明。建立了两种免疫缺陷型终末期视网膜变性小鼠模型，免疫缺陷型宿主允许移植人胚胎干细胞源性视网膜薄片，移植后人胚胎干细胞源性视网膜薄片长期存活并成熟，移植后记录了变性宿主视网膜的光反应。Mandai和同事开发了具有终末期视网膜变性的免疫缺陷小鼠系，并在其中测试了人ESC-的功能成熟移植后的视网膜组织。在移植区域检测到宿主视网膜神经节细胞的光反应活性，这表明这些移植组织的功能潜力。
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. Two mouse models of immunodeficient end-stage retinal degeneration were established Immunodeficient host permitted transplantation of human ESC-derived retinal sheets Transplanted human ESC-derived retinal sheets survived long term and maturated After transplantation, light responses were recorded from the degenerated host retina In this article, Mandai and colleagues developed the immune-deficient mouse lines with end-stage retinal degeneration and tested in them the functional maturation of human ESC-derived retinal tissues after transplantation. Light-responsive activities in the host retinal ganglion cells were detected in the transplanted area, which suggests functional potency of these graft tissues.
登录
查看更多内容
影响因子：
4.4
作者：
Kaewkhaw R;Swaroop M;Homma K;Nakamura J;Brooks M;Kaya KD;Chaitankar V;Michael S;Tawa G;Zou J;Rao M;Zheng W;Cogliati T;Swaroop A
通讯作者：
Swaroop A
影响因子：
64.8
作者：
Pearson, R. A.;Barber, A. C.;Rizzi, M.;Hippert, C.;Xue, T.;West, E. L.;Duran, Y.;Smith, A. J.;Chuang, J. Z.;Azam, S. A.;Luhmann, U. F. O.;Benucci, A.;Sung, C. H.;Bainbridge, J. W.;Carandini, M.;Yau, K. -W.;Sowden, J. C.;Ali, R. R.
通讯作者：
Ali, R. R.
影响因子：
5.9
作者：
Assawachananont, Juthaporn;Mandai, Michiko;Okamoto, Satoshi;Yamada, Chikako;Eiraku, Mototsugu;Yonemura, Shigenobu;Sasai, Yoshiki;Takahashi, Masayo
通讯作者：
Takahashi, Masayo
影响因子：
1.8
作者：
Kim, Ki Hean;Puoris'haag, Mehron;de Boer, Johannes F.
通讯作者：
de Boer, Johannes F.
影响因子：
3.3
作者：
Larsson, LC;Czech, KA;Widner, H
通讯作者：
Widner, H