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Maximizing Functional Photoreceptor Differentiation From Adult Human Retinal Stem Cells

2009; Oxford University Press; Volume: 28; Issue: 3 Linguagem: Inglês

10.1002/stem.279

1549-4918

Tomoyuki Inoue, Brenda L.K. Coles, Kim Dorval, Rod Bremner, Yasumasa Bessho, Ryoichiro Kageyama, Shinjiro Hino, Masao Matsuoka, Cheryl M. Craft, Roderick R. McInnes, François Tremblay, Glen T. Prusky, Derek van der Kooy,

Photochromic and Fluorescence Chemistry

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.