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

Kamil Kruczek | Zendy; Anai Gonzalez-Cordero | Zendy; Debbie Goh | Zendy; Arifa Naeem | Zendy; Mindaugas Jonikas | Zendy; Samuel J.I. Blackford | Zendy; Magdalena Kloc | Zendy; Yanaí Durán | Zendy; Anastasios Georgiadis | Zendy; Robert D. Sampson | Zendy; Ryea Maswood | Zendy; Alexander J. Smith | Zendy; Sarah Decembrini | Zendy; Yvan Arsenijévic | Zendy; Jane C. Sowden | Zendy; R. A. Pearson | Zendy; Emma L. West | Zendy; Robin R. Ali | Zendy

Open Access

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

Author(s) -

Kamil Kruczek,

Anai Gonzalez-Cordero,

Debbie Goh,

Arifa Naeem,

Mindaugas Jonikas,

Samuel J.I. Blackford,

Magdalena Kloc,

Yanaí Durán,

Anastasios Georgiadis,

Robert D. Sampson,

Ryea Maswood,

Alexander J. Smith,

Sarah Decembrini,

Yvan Arsenijévic,

Jane C. Sowden,

R. A. Pearson,

Emma L. West,

Robin R. Ali

Publication year - 2017

Publication title -

stem cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.207

H-Index - 76

ISSN - 2213-6711

DOI - 10.1016/j.stemcr.2017.04.030

Subject(s) - biology , transplantation , microbiology and biotechnology , embryonic stem cell , retinal degeneration , stem cell , retina , photoreceptor cell , cellular differentiation , retinal , progenitor cell , visual phototransduction , immunology , neuroscience , medicine , genetics , gene , biochemistry

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 β2-positive precursors and, subsequently, photoreceptors exhibiting cone-specific phototransduction-related 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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research