Maximizing Functional Photoreceptor Differentiation From Adult Human Retinal Stem Cells-Reference-Cited by-同舟云学术

Maximizing Functional Photoreceptor Differentiation From Adult Human Retinal Stem Cells

Published:2009-12-11 Issue:3 Volume:28 Page:489-500
ISSN:1066-5099
Container-title:Stem Cells
language:en
Short-container-title:

Author:

Inoue Tomoyuki¹²,Coles Brenda L.K.¹,Dorval Kim³,Bremner Rod³,Bessho Yasumasa⁴,Kageyama Ryoichiro⁵,Hino Shinjiro⁶,Matsuoka Masao⁶,Craft Cheryl M.⁷,McInnes Roderick R.⁸,Tremblay Francois⁹,Prusky Glen T.¹⁰,van der Kooy Derek¹

Affiliation:

1. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

2. Department of Ophthalmology, Osaka University Medical School, Japan

3. Departments of Ophthalmology and Lab Med & Pathobiology, University of Toronto, Toronto, Ontario, Canada

4. Department of Gene Regulation Research, Graduate School of Biological Sciences Nara Institute of Science and Technology, Ikoma, Japan

5. Department of Cell Biology, Institute for Virus Research, Kyoto University, Kawaracho, Kyoto, Japan

6. Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kawaracho, Kyoto, Japan

7. Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

8. Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada, and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

9. Department of Ophthalmology, Dalhousie University, Halifax, Nova Scotia, Canada

10. Department of Physiology and Biophysics, Weill Medical College of Cornell University, White Plains, New York, USA

Abstract

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.

Funder

NIH

Canadian Institutes of Health Research

Lincy Foundation

Foundation Fighting Blindness of Canada

Canadian Stem Cell Network

Steinbach Foundation

Japan Society for the Promotion of Science

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine