Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application.

Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application.
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DOI:
10.1016/j.stemcr.2013.12.007
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发表时间:
2014-02-11
期刊:
影响因子:
5.9
通讯作者:
Takahashi, Masayo
Takahashi, Masayo
中科院分区:
医学1区
文献类型:
--
作者:
Kamao, Hiroyuki;Mandai, Michiko;Okamoto, Satoshi;Sakai, Noriko;Suga, Akiko;Sugita, Sunao;Kiryu, Junichi;Takahashi, Masayo

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视网膜相关性黄斑变性(AMD)部分由于视网膜色素上皮(RPE)的年龄依赖性损害而导致严重的视力损害。有人认为,自体人诱导多能干细胞(hiPSC)可能是产生移植RPE的有用细胞来源。我们生成了优化的hiPSC衍生的RPE(hiPSC-RPE)细胞片层,以满足临床使用要求,包括质量、数量、一致性和安全性。这些细胞片层作为单层细胞产生,没有任何人工支架,表达典型的RPE标记物,形成紧密连接,表现出生长因子的极化分泌,并显示吞噬能力和基因表达模式类似于天然RPE。此外,在移植后,自体非人灵长类iPSC-RPE细胞片未显示免疫排斥或肿瘤形成。这些结果表明,自体hiPSC-RPE细胞片可以作为用于AMD的组织替代疗法的有用形式的移植物。hiPSC-RPE细胞片层显示出与天然RPE相似的特征。hiPSC-RPE片层足以移植患者。所有hiPSC-RPE显示出与天然RPE相似的基因表达模式。非人灵长类动物iPSC-RPE细胞片层显示出无排斥反应或肿瘤。作为这种疾病的潜在治疗方法,Takahashi及其同事产生了优化的hiPSC-RPE细胞片,以满足临床使用要求,包括质量,数量,一致性和安全性。hiPSC-RPE细胞片可作为用于年龄相关性黄斑变性组织替代疗法的有用形式的移植物。
Age-related macular degeneration (AMD) causes severe visual impairment due in part to age-dependent impairment of retinal pigment epithelium (RPE). It has been suggested that autologous human induced pluripotent stem cells (hiPSCs) may represent a useful cell source for the generation of graft RPE. We generated hiPSC-derived RPE (hiPSC-RPE) cell sheets optimized to meet clinical use requirements, including quality, quantity, consistency, and safety. These cell sheets are generated as a monolayer of cells without any artificial scaffolds, express typical RPE markers, form tight junctions that exhibit polarized secretion of growth factors, and show phagocytotic ability and gene-expression patterns similar to those of native RPE. Additionally, upon transplantation, autologous nonhuman primate iPSC-RPE cell sheets showed no immune rejection or tumor formation. These results suggest that autologous hiPSC-RPE cell sheets may serve as a useful form of graft for use in tissue replacement therapy for AMD. hiPSC-RPE cell sheets show characteristics similar to those of native RPE A hiPSC-RPE sheet is sufficient to transplant a patient All hiPSC-RPEs show gene-expression patterns similar to native RPE Autologous nonhuman primate iPSC-RPE cell sheets show no rejection or tumor Age-related macular degeneration is a leading cause of blindness in the elderly worldwide. As a potential treatment for this disease, Takahashi and colleagues generated hiPSC-RPE cell sheets optimized to meet clinical use requirements, including quality, quantity, consistency, and safety. hiPSC-RPE cell sheets may serve as a useful form of graft for use in tissue replacement therapy for age-related macular degeneration.
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