Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors into a Mouse Model of End-Stage Retinal Degeneration

被引：80

作者：

Kruczek, Kamil ^{[1
]}

Gonzalez-Cordero, Anai ^{[1
]}

Goh, Debbie ^{[1
]}

Naeem, Arifa ^{[1
]}

Jonikas, Mindaugas ^{[1
]}

Blackford, Samuel J. I. ^{[1
]}

Kloc, Magdalena ^{[1
]}

Duran, Yanai ^{[1
]}

Georgiadis, Anastasios ^{[1
]}

Sampson, Robert D. ^{[1
]}

Maswood, Ryea N. ^{[1
]}

Smith, Alexander J. ^{[1
]}

Decembrini, Sarah ^{[2
]}

Arsenijevic, Yvan ^{[2
]}

Sowden, Jane C. ^{[3
]}

Pearson, Rachael A. ^{[1
]}

West, Emma L. ^{[1
]}

Ali, Robin R. ^{[1
,4
]}

机构：

[1] UCL Inst Ophthalmol, Dept Genet, London EC1V 9EL, England

[2] Univ Lausanne, Jules Gonin Eye Hosp, Dept Ophthalmol, CH-1004 Lausanne, Switzerland

[3] UCL, UCL Great Ormond St Inst Child Hlth, Stem Cells & Regenerat Med Sect, London WC1N 1EH, England

[4] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, City Rd, London EC1V 2PD, England

来源：

STEM CELL REPORTS | 2017年 / 8卷 / 06期

基金：

英国医学研究理事会; 欧洲研究理事会;

关键词：

THYROID-HORMONE RECEPTOR; DEVELOPMENTAL EXPRESSION; ROD PHOTORECEPTORS; MAMMALIAN RETINA; PROGENITOR CELLS; RESTORATION; PRECURSORS; FATE; MICE; REPLACEMENT;

D O I：

10.1016/j.stemcr.2017.04.030

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The loss of cone photoreceptors that mediate daylight vision represents a leading cause of blindness, for which cell replacement by transplantation offers a promising treatment strategy. Here, we characterize cone differentiation in retinas derived from mouse embryonic stem cells (mESCs). Similar to in vivo development, a temporal pattern of progenitor marker expression is followed by the differentiation of early thyroid hormone receptor beta 2-positive precursors and, subsequently, photoreceptors exhibiting cone-specific phototransductionrelated proteins. We establish that stage-specific inhibition of the Notch pathway increases cone cell differentiation, while retinoic acid signaling regulates cone maturation, comparable with their actions in vivo. MESC-derived cones can be isolated in large numbers and transplanted into adult mouse eyes, showing capacity to survive and mature in the subretinal space of Aipl1(-/-) mice, a model of end-stage retinal degeneration. Together, this work identifies a robust, renewable cell source for cone replacement by purified cell suspension transplantation.

引用

页码：1659 / 1674

页数：16

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