建立功能性视网膜培养的进展与希望:诱导多能干细胞分化为视网膜神经元的进展与前景。
Establishing Functional Retina in a Dish: Progress and Promises of Induced Pluripotent Stem Cell-Based Retinal Neuron Differentiation.
发表日期:2023 Sep 04
作者:
Nonthaphat Kent Wong, Shea Ping Yip, Chien-Ling Huang
来源:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
摘要:
人眼在视觉感知中扮演重要角色,但是各种视网膜退行性疾病,比如色素性视网膜炎(RP)、青光眼和老年性黄斑变性(AMD)可能导致视力丧失或失明。虽然在了解视网膜发育和临床研究方面取得了进展,但目前的治疗方法仍无法治愈或逆转这些退行性疾病。动物模型与人类的相似性有限,获取人眼组织样本也面临伦理和法律考量的挑战。因此,研究人员转向干细胞为基础的方法,特别是通过诱导多能干细胞(iPSCs)来生成不同视网膜细胞群落,发展细胞替代疗法。iPSCs为研究人类视网膜发育关键阶段和疾病特异性机制提供了新的平台。干细胞技术使得各种视网膜细胞类型的生产成为可能,包括视网膜神经节细胞(RGCs)和光感受器,视网膜器官样结构的发展也成为研究视网膜神经元分化和建立视网膜疾病模型的有价值的离体工具。本综述将专注于描述分化iPSCs产生视网膜神经元的方案、培养条件和技术。此外,本文还强调了对分化细胞进行分子和功能验证的重要性。
The human eye plays a critical role in vision perception, but various retinal degenerative diseases such as retinitis pigmentosa (RP), glaucoma, and age-related macular degeneration (AMD) can lead to vision loss or blindness. Although progress has been made in understanding retinal development and in clinical research, current treatments remain inadequate for curing or reversing these degenerative conditions. Animal models have limited relevance to humans, and obtaining human eye tissue samples is challenging due to ethical and legal considerations. Consequently, researchers have turned to stem cell-based approaches, specifically induced pluripotent stem cells (iPSCs), to generate distinct retinal cell populations and develop cell replacement therapies. iPSCs offer a novel platform for studying the key stages of human retinogenesis and disease-specific mechanisms. Stem cell technology has facilitated the production of diverse retinal cell types, including retinal ganglion cells (RGCs) and photoreceptors, and the development of retinal organoids has emerged as a valuable in vitro tool for investigating retinal neuron differentiation and modeling retinal diseases. This review focuses on the protocols, culture conditions, and techniques employed in differentiating retinal neurons from iPSCs. Furthermore, it emphasizes the significance of molecular and functional validation of the differentiated cells.