Open AccessMaximizing Functional Photoreceptor Differentiation From Adult Human Retinal Stem Cells
Author(s) -
Inoue Tomoyuki,
Coles Brenda L.K.,
Dorval Kim,
Bremner Rod,
Bessho Yasumasa,
Kageyama Ryoichiro,
Hino Shinjiro,
Matsuoka Masao,
Craft Cheryl M.,
McInnes Roderick R.,
Tremblay Francois,
Prusky Glen T.,
van der Kooy Derek
Publication year - 2010
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.279
Subject(s) - biology , retinal , transducin , microbiology and biotechnology , stem cell , retina , transcription factor , cellular differentiation , visual phototransduction , genetics , gene , neuroscience , rhodopsin , botany
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. S TEM C ELLS 2010;28:489–500