Recapitulation of Human Retinal Development from Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors.
Recapitulation of Human Retinal Development from Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors.
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DOI：
10.1016/j.stemcr.2017.07.022
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发表时间：
2017-09-12
影响因子：
5.9
通讯作者：
Ali RR
中科院分区：
文献类型：
--
作者：
Gonzalez-Cordero A;Kruczek K;Naeem A;Fernando M;Kloc M;Ribeiro J;Goh D;Duran Y;Blackford SJI;Abelleira-Hervas L;Sampson RD;Shum IO;Branch MJ;Gardner PJ;Sowden JC;Bainbridge JWB;Smith AJ;West EL;Pearson RA;Ali RR
来自新生儿视网膜或多能干细胞（PSC）的视杆细胞移植可以恢复遗传性失明小鼠模型中视杆细胞介导的视觉功能。然而，人类更多地依赖于日光、颜色和高敏锐度视觉所需的锥状光感受器。事实上，涉及视锥细胞损失的黄斑视网膜病变是失明的主要原因。开发用于黄斑病变的基于干细胞的疗法的重要步骤是能够从可再生来源产生可移植的人类视锥细胞。在这里，我们报告了一种改进的2D/3D协议，用于生成hPSC衍生的神经视网膜囊泡，其具有良好形成的ONL样结构，包含圆锥体和杆状体，其具有内段和连接纤毛、新生外段和突触前结构。这种分化系统重现了人类感光细胞的发育，允许分离和移植纯人群的阶段匹配的锥细胞。纯化的人长/中视锥细胞存活并并入成年小鼠视网膜内，支持光感受器移植用于治疗视网膜变性的潜力。hPSC衍生的光感受器以类似于人类发育的模式表达标志物2D/3D分化方案产生足够的视锥用于移植，移植后hPSC衍生的视锥并入成人视网膜中Gonzalez-Cordero et al.描述了从人多能干细胞稳健地产生光感受器的方案，并报道了人视锥光感受器的纯群体的移植和它们掺入受体成年鼠神经视网膜中。
Transplantation of rod photoreceptors, derived either from neonatal retinae or pluripotent stem cells (PSCs), can restore rod-mediated visual function in murine models of inherited blindness. However, humans depend more upon cone photoreceptors that are required for daylight, color, and high-acuity vision. Indeed, macular retinopathies involving loss of cones are leading causes of blindness. An essential step for developing stem cell-based therapies for maculopathies is the ability to generate transplantable human cones from renewable sources. Here, we report a modified 2D/3D protocol for generating hPSC-derived neural retinal vesicles with well-formed ONL-like structures containing cones and rods bearing inner segments and connecting cilia, nascent outer segments, and presynaptic structures. This differentiation system recapitulates human photoreceptor development, allowing the isolation and transplantation of a pure population of stage-matched cones. Purified human long/medium cones survive and become incorporated within the adult mouse retina, supporting the potential of photoreceptor transplantation for treating retinal degeneration. hPSC-derived photoreceptors express markers in a pattern similar to human development 2D/3D differentiation protocol generates sufficient cones for transplantation hPSC-derived cones incorporate into the adult retina following transplantation Gonzalez-Cordero et al. describe a protocol for the robust generation of photoreceptors from human pluripotent stem cells and report the transplantation of a pure population of human cone photoreceptors and their incorporation into the recipient adult murine neural retina.
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影响因子：
25
作者：
Kinouchi, R;Takeda, M;Chen, DF
通讯作者：
Chen, DF
MANF免疫调节可促进视网膜的组织修复和再生成功。
DOI：
10.1126/science.aaf3646
发表时间：
2016-07-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Neves J;Zhu J;Sousa-Victor P;Konjikusic M;Riley R;Chew S;Qi Y;Jasper H;Lamba DA
通讯作者：
Lamba DA
影响因子：
30.8
作者：
Mears, AJ;Kondo, M;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