Generation of Transplantable Retinal Photoreceptors from a Current Good Manufacturing Practice-Manufactured Human Induced Pluripotent Stem Cell Line.
Generation of Transplantable Retinal Photoreceptors from a Current Good Manufacturing Practice-Manufactured Human Induced Pluripotent Stem Cell Line.
复制标题
从当前良好生产规范制造的人类诱导多能干细胞系中产生可移植的视网膜感光器。
DOI：
10.1002/sctm.17-0205
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发表时间：
2018
影响因子：
6
通讯作者：
Lamba,DeepakAshok
中科院分区：
文献类型：
--
作者：
Zhu,Jie;Reynolds,Joseph;Garcia,Thelma;Cifuentes,Helen;Chew,Shereen;Zeng,Xianmin;Lamba,DeepakAshok
视网膜变性常导致感光细胞的丧失，从而导致永久性视力丧失。使用人类体细胞衍生的诱导多能干细胞（iPSC）产生可移植的视网膜光感受器有望通过用健康和功能性的光感受器替换受损或功能障碍的天然光感受器来治疗各种视网膜退行性疾病。建立有效的方法来生产视网膜细胞，包括在化学定义的条件下使用目前的良好生产规范（cGMP）制造的人iPSC系的光感受器是至关重要的细胞替代疗法推进到临床。在这项研究中，我们使用了在符合cGMP的条件下从CD 34+脐带血细胞衍生的人iPSC系（NCL-1）。使用基于小分子的视网膜诱导方案将细胞分化成视网膜细胞。我们表明，视网膜细胞，包括光感受器，视网膜色素上皮细胞和视杯样视网膜类器官可以从NCL-1 iPSC系产生。此外，我们表明，视网膜下移植到免疫缺陷的宿主小鼠眼睛，视网膜细胞成功地整合到感光层，并发展成成熟的光感受器。这项研究提供了强有力的证据，证明可以从cGMP制造的人类iPSC系中产生可移植的光感受器，用于临床应用。
AbstractRetinal degeneration often results in the loss of light-sensing photoreceptors, which leads to permanent vision loss. Generating transplantable retinal photoreceptors using human somatic cell-derived induced pluripotent stem cells (iPSCs) holds promise to treat a variety of retinal degenerative diseases by replacing the damaged or dysfunctional native photoreceptors with healthy and functional ones. Establishment of effective methods to produce retinal cells including photoreceptors in chemically defined conditions using current Good Manufacturing Practice (cGMP)-manufactured human iPSC lines is critical for advancing cell replacement therapy to the clinic. In this study, we used a human iPSC line (NCL-1) derived under cGMP-compliant conditions from CD34+ cord blood cells. The cells were differentiated into retinal cells using a small molecule-based retinal induction protocol. We show that retinal cells including photoreceptors, retinal pigmented epithelial cells and optic cup-like retinal organoids can be generated from the NCL-1 iPSC line. Additionally, we show that following subretinal transplantation into immunodeficient host mouse eyes, retinal cells successfully integrated into the photoreceptor layer and developed into mature photoreceptors. This study provides strong evidence that transplantable photoreceptors can be generated from a cGMP-manufactured human iPSC line for clinical applications.