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将诱导多能干细胞从实验室转化到临床:在视网膜疾病中的应用。

Translating induced pluripotent stem cells from bench to bedside: application to retinal diseases.

机构信息

Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, NIHR Biomedical Research Centre, University of Oxford, Oxford OX3 9DU, UK.

出版信息

Curr Gene Ther. 2013 Apr;13(2):139-51. doi: 10.2174/1566523211313020008.

Abstract

Induced pluripotent stem cells (iPSc) are a scientific and medical frontier. Application of reprogrammed somatic cells for clinical trials is in its dawn period; advances in research with animal and human iPSc are paving the way for retinal therapies with the ongoing development of safe animal cell transplantation studies and characterization of patient- specific and disease-specific human iPSc. The retina is an optimal model for investigation of neural regeneration; amongst other advantageous attributes, it is the most accessible part of the CNS for surgery and outcome monitoring. A recent clinical trial showing a degree of visual restoration via a subretinal electronic prosthesis implies that even a severely degenerate retina may have the capacity for repair after cell replacement through potential plasticity of the visual system. Successful differentiation of neural retina from iPSc and the recent generation of an optic cup from human ESc invitro increase the feasibility of generating an expandable and clinically suitable source of cells for human clinical trials. In this review we shall present recent studies that have propelled the field forward and discuss challenges in utilizing iPS cell derived retinal cells as reliable models for clinical therapies and as a source for clinical cell transplantation treatment for patients suffering from genetic retinal disease.

摘要

诱导多能干细胞(iPSC)是科学和医学的前沿领域。重编程体细胞在临床试验中的应用正处于起步阶段;随着对动物和人类 iPSC 的研究进展,通过正在进行的安全动物细胞移植研究和对患者特异性和疾病特异性人类 iPSC 的特征描述,为视网膜疗法铺平了道路。视网膜是研究神经再生的理想模型;除了其他有利的特性外,它是 CNS 中最容易进行手术和结果监测的部分。最近的一项临床试验表明,通过视网膜下电子假体可以恢复一定程度的视力,这意味着即使是严重退化的视网膜,在通过细胞替代实现潜在的可塑性后,也可能有修复的能力。iPSC 中神经视网膜的成功分化和最近从人类 ESC 体外生成的视神经杯增加了生成可扩展和临床适用的细胞来源的可行性,以进行人类临床试验。在这篇综述中,我们将介绍推动该领域发展的最新研究,并讨论利用 iPSC 衍生的视网膜细胞作为临床治疗可靠模型的挑战,以及作为治疗遗传性视网膜疾病患者的临床细胞移植治疗的来源的挑战。

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