Maximizing functional photoreceptor differentiation from adult human retinal stem cells

Tomoyuki Inoue; Brenda L.K. Coles; K. I.M. Dorval; R. O.D. Bremner; Yasumasa Bessho; Ryoichiro Kageyama; Shinjiro Hino; Masao Matsuoka; Cheryl M. Craft; Roderick R. Mcinnes; Francois Tremblay; Glen T. Prusky; Derek Van Der Kooy

doi:10.1002/stem.279

Maximizing functional photoreceptor differentiation from adult human retinal stem cells

Tomoyuki Inoue, Brenda L.K. Coles, K. I.M. Dorval, R. O.D. Bremner, Yasumasa Bessho, Ryoichiro Kageyama, Shinjiro Hino, Masao Matsuoka, Cheryl M. Craft, Roderick R. Mcinnes, Francois Tremblay, Glen T. Prusky, Derek Van Der Kooy

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

70 Citas (Scopus)

Resumen

Retinal stem cells (RSCs) are present in the ciliary margin of the adult human eye and can give rise to all retinal cell types. Here we show that modulation of retinal transcription factor gene expression in human RSCs greatly enriches photoreceptor progeny, and that strong enrichment was obtained with the combined transduction of OTX2 and CRX together with the modulation of CHX10. When these genetically modified human RSC progeny are transplanted into mouse eyes, their retinal integration and differentiation is superior to unmodified RSC progeny. Moreover, electrophysiologic and behavioral tests show that these transplanted cells promote functional recovery in transducin mutant mice. This study suggests that gene modulation in human RSCs may provide a source of photoreceptor cells for the treatment of photoreceptor disease.

Idioma original	English
Páginas (desde-hasta)	489-500
Número de páginas	12
Publicación	Stem Cells
Volumen	28
N.º	3
DOI	https://doi.org/10.1002/stem.279
Estado	Published - mar. 31 2010

Nota bibliográfica

Funding Information:
This study was supported in part by grants from the National Institutes of Heath (DK-45923), National Kidney Foundation of Texas, and a Grant-in-aid from the American Heart Association. This work as done during the tenure of an Established Investigatorship from the American Heart Association (RAS). Y. Kohda was supported by a fellowship award from the National Kidney Foundation.

ASJC Scopus Subject Areas

Molecular Medicine
Developmental Biology
Cell Biology

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abstract = "Retinal stem cells (RSCs) are present in the ciliary margin of the adult human eye and can give rise to all retinal cell types. Here we show that modulation of retinal transcription factor gene expression in human RSCs greatly enriches photoreceptor progeny, and that strong enrichment was obtained with the combined transduction of OTX2 and CRX together with the modulation of CHX10. When these genetically modified human RSC progeny are transplanted into mouse eyes, their retinal integration and differentiation is superior to unmodified RSC progeny. Moreover, electrophysiologic and behavioral tests show that these transplanted cells promote functional recovery in transducin mutant mice. This study suggests that gene modulation in human RSCs may provide a source of photoreceptor cells for the treatment of photoreceptor disease.",

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AU - Coles, Brenda L.K.

AU - Dorval, K. I.M.

AU - Bremner, R. O.D.

AU - Bessho, Yasumasa

AU - Kageyama, Ryoichiro

AU - Hino, Shinjiro

AU - Matsuoka, Masao

AU - Craft, Cheryl M.

AU - Mcinnes, Roderick R.

AU - Tremblay, Francois

AU - Prusky, Glen T.

AU - Van Der Kooy, Derek

N1 - Funding Information: This study was supported in part by grants from the National Institutes of Heath (DK-45923), National Kidney Foundation of Texas, and a Grant-in-aid from the American Heart Association. This work as done during the tenure of an Established Investigatorship from the American Heart Association (RAS). Y. Kohda was supported by a fellowship award from the National Kidney Foundation.

PY - 2010/3/31

Y1 - 2010/3/31

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AB - Retinal stem cells (RSCs) are present in the ciliary margin of the adult human eye and can give rise to all retinal cell types. Here we show that modulation of retinal transcription factor gene expression in human RSCs greatly enriches photoreceptor progeny, and that strong enrichment was obtained with the combined transduction of OTX2 and CRX together with the modulation of CHX10. When these genetically modified human RSC progeny are transplanted into mouse eyes, their retinal integration and differentiation is superior to unmodified RSC progeny. Moreover, electrophysiologic and behavioral tests show that these transplanted cells promote functional recovery in transducin mutant mice. This study suggests that gene modulation in human RSCs may provide a source of photoreceptor cells for the treatment of photoreceptor disease.

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Maximizing functional photoreceptor differentiation from adult human retinal stem cells

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