Transplanted human induced pluripotent stem cells-derived retinal ganglion cells embed within mouse retinas and are electrophysiologically functional

被引：14

作者：

Vrathasha, Vrathasha ^{[1
]}

Nikonov, Sergei ^{[1
,2
,3
]}

Bell, Brent Allen ^{[1
,2
,3
]}

He, Jie ^{[1
]}

Bungatavula, Yajat ^{[1
]}

Uyhazi, Katherine Elizabeth ^{[1
,2
,3
]}

Chavali, Venkata Ramana Murthy ^{[1
,2
,3
]}

机构：

[1] Univ Penn, Perelman Ctr Adv Med, Scheie Eye Inst, Philadelphia, PA 19104 USA

[2] Univ Penn, Ctr Adv Retinal & Ocular Therapeut CAROT, Philadelphia, PA 19104 USA

[3] Univ Penn, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA

来源：

ISCIENCE | 2022年 / 25卷 / 11期

基金：

美国国家卫生研究院;

关键词：

OPEN-ANGLE GLAUCOMA; INTERNAL LIMITING MEMBRANE; CONE PHOTORECEPTORS; PROGENITOR CELLS; GENERATION; DIFFERENTIATION; PREVALENCE; TRANSDUCTION; PRECURSORS; EXPRESSION;

D O I：

10.1016/j.isci.2022.105308

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Glaucoma is an optic neuropathy characterized by permanent visual field loss caused by the death of retinal ganglion cells (RGCs) and it is the leading cause of irreversible blindness worldwide. Consequently, there is an unmet need for the development of new strategies for its treatment. We investigated RGC replacement therapy as a treatment for ganglion cell loss. Human-induced pluripotent stem cells (hiPSCs) were differentiated into mature, functional RGCs in vitro, labeled with AAV2.7m8-SNCG-eGFP, and transplanted intravitreally in wild-type 4-month-old C57BL/6J mice. Survival of the transplanted hiPSC-RGCs was assessed by color fundus photography and histological studies confirmed the localization of the transplanted hiPSC-RGCs within the retina. Two-photon live imaging of retinal explants and electrophysiological studies confirmed that the morphology and function of the transplanted hiPSC-RGCs were similar to native RGCs. These experiments will provide key strategies to enhance the efficiency of stem cell replacement therapy for neurodegenerative diseases, including glaucoma.

引用

页数：23

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