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人诱导多能干细胞衍生的视网膜神经节细胞在组织工程支架上生长出树突状分支和功能性轴突。

HiPSC-derived retinal ganglion cells grow dendritic arbors and functional axons on a tissue-engineered scaffold.

机构信息

State Key Laboratory of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yet-Sen University, Guangzhou, Guangdong, China.

Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Yet-Sen University, Guangzhou, Guangdong, China.

出版信息

Acta Biomater. 2017 May;54:117-127. doi: 10.1016/j.actbio.2017.02.032. Epub 2017 Feb 17.

DOI:10.1016/j.actbio.2017.02.032
PMID:28216299
Abstract

UNLABELLED

Numerous therapeutic procedures in modern medical research rely on the use of tissue engineering for the treatment of retinal diseases. However, the cell source and the transplantation method are still a limitation. Previously, it was reported that a self-organizing three-dimensional neural retina can be induced from human-induced pluripotent stem cells (hiPSCs). In this study, we disclose the generation of retinal ganglion cells (RGCs) from the neural retina and their seeding on a biodegradable poly (lactic-co-glycolic acid) (PLGA) scaffold to create an engineered RGC-scaffold biomaterial. Moreover, we explored the dendritic arbor, branching point, functional axon and action potential of the biomaterial. Finally, the cell-scaffold was transplanted into the intraocular environment of rabbits and rhesus monkeys.

STATEMENT OF SIGNIFICANCE

As a part of the mammalian central nervous system (CNS), the retinal ganglion cell (RGC) shows little regenerative capacity. With the use of medical biomaterial for cells seeding and deliver, a new domain is now emerging that uses tissue engineering therapy for retinal disease. However, previous studies utilized RGCs from rodent model, which has limitations for human disease treatment. In the present study, we generated RGCs from hiPSCs-3D neural retina and then seeded these RGCs on PLGA scaffold to create an engineered RGC-scaffold biomaterial. Moreover, we assessed the transplantation method for biomaterial in vivo. Our study provides a technique to produce the engineered human RGC-scaffold biomaterial.

摘要

未加标签

现代医学研究中的许多治疗程序都依赖于组织工程来治疗视网膜疾病。然而,细胞来源和移植方法仍然是一个限制。以前有报道称,从人诱导多能干细胞(hiPSCs)可以诱导出具有自我组织的三维神经视网膜。在这项研究中,我们从神经视网膜中产生视网膜神经节细胞(RGCs),并将其播种到可生物降解的聚(乳酸-共-羟基乙酸)(PLGA)支架上,以创建工程 RGC-支架生物材料。此外,我们探索了生物材料的树突分支、分支点、功能轴突和动作电位。最后,将细胞-支架移植到兔和恒河猴的眼内环境中。

意义声明

作为哺乳动物中枢神经系统(CNS)的一部分,视网膜神经节细胞(RGC)表现出很少的再生能力。随着细胞播种和传递的医用生物材料的使用,一个新的领域正在出现,该领域使用组织工程疗法治疗视网膜疾病。然而,以前的研究使用了来自啮齿动物模型的 RGC,这对人类疾病的治疗有一定的局限性。在本研究中,我们从 hiPSCs-3D 神经视网膜中产生 RGCs,然后将这些 RGCs播种到 PLGA 支架上,以创建工程 RGC-支架生物材料。此外,我们评估了生物材料在体内的移植方法。我们的研究为产生工程化的人 RGC-支架生物材料提供了一种技术。

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