title: HiPSC-derived retinal ganglion cells grow dendritic arbors and functional axons on a tissue-engineered scaffold.
abstract: 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.
  
  
  
  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.
authors.affiliation: State Key Laboratory of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yet-Sen University, Guangzhou, Guangdong, China.
authors.forename: Kangjun
authors.initials: K
authors.lastname: Li
authors.affiliation: State Key Laboratory of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yet-Sen University, Guangzhou, Guangdong, China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yet-Sen University, Guangzhou, Guangdong, China.
authors.forename: Sijing
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yet-Sen University, Guangzhou, Guangdong, China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yet-Sen University, Guangzhou, Guangdong, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.affiliation: State Key Laboratory of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yet-Sen University, Guangzhou, Guangdong, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Yet-Sen University, Guangzhou, Guangdong, China.
authors.forename: Song
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Yet-Sen University, Guangzhou, Guangdong, China.
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Gu
authors.affiliation: Bai Duoan Medical Equipment Company, Qihe, Shandong, China.
authors.forename: Shoutao
authors.initials: S
authors.lastname: Lu
authors.affiliation: Bai Duoan Medical Equipment Company, Qihe, Shandong, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yet-Sen University, Guangzhou, Guangdong, China.
authors.forename: Yantao
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yet-Sen University, Guangzhou, Guangdong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhuang
authors.affiliation: State Key Laboratory of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yet-Sen University, Guangzhou, Guangdong, China.
authors.forename: Yehong
authors.initials: Y
authors.lastname: Zhuo
authors.affiliation: State Key Laboratory of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yet-Sen University, Guangzhou, Guangdong, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yet-Sen University, Guangzhou, Guangdong, China. Electronic address: gejian@mail.sysu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Ge
mesh_terms: D001369:Axons / Q000378:metabolism*; D002460:Cell Line; D003712:Dendrites / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*
keywords: Biomaterials; Human-induced pluripotent stem cells (hiPSCs); Retina; Retinal ganglion cells (RGCs); Tissue engineering