Journal
TRANSPLANTATION
Volume 89, Issue 8, Pages 911-919Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e3181d45a61
Keywords
Embryonic stem cell; Retinal pigment epithelium; RPE65; Retinal degeneration
Categories
Funding
- NIH [EY013435, R01EY018213]
- Research to Prevent Blindness, New York City, NY
- Foundation Fighting Blindness
- Schneeweiss Stargardt Fund
- Starr Foundation
- Prevent Blindness Award and Foundation
- Dennis W. Jahnigen Award of the American Geriatrics Society
- Joel Hoffman Fund
- Gale and Richard Siegel Stem Cell Fund
- Charles Culpeper Scholarship
- Schneeweiss Stem Cell Fund
- Irma T. Hirschl Charitable Trust
- Bernard and Anne Spitzer Stem Cell Fund
- Barbara and Donald Jonas Family Fund
- Eye Surgery Fund and Professor Gertrude Rothschild Stem Cell Foundation
- Taiwan National Science Council [NSC-096-2917-I-002-105, 98-2314-B-182A-078-]
- Chang Gung Memorial Hospital [CM-RPG360571, 360572]
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Background. To study whether C57BL/6J-Tyr(c-2j)/J (C2J) mouse embryonic stem (ES) cells can differentiate into retinal pigment epithelial (RPE) cells in vitro and then restore retinal function in a model for retinitis pigmentosa: Rpe65(rd12)/Rpe65(rd12) C57BL6 mice. Methods. Yellow fluorescent protein (YFP)-labeled C2J ES cells were induced to differentiate into RPE-like structures on PA6 feeders. RPE-specific markers are expressed from differentiated cells in vitro. After differentiation, ES cell-derived RPE-like cells were transplanted into the subretinal space of postnatal day 5 Rpe65(rd12)/Rpe65(rd12) mice. Live imaging of YFP-labeled C2J ES cells demonstrated survival of the graft. Electroretinograms (ERGs) were performed on transplanted mice to evaluate the functional outcome of transplantation. Results. RPE-like cells derived from ES cells sequentially express multiple RPE-specific markers. After transplantation, YFP-labeled cells can be tracked with live imaging for as long as 7 months. Although more than half of the mice were complicated with retinal detachments or tumor development, one fourth of the mice showed increased electroretinogram responses in the transplanted eyes. Rpe65(rd12)/Rpe65(rd12) mice transplanted with RPE-like cells showed significant visual recovery during a 7-month period, whereas those injected with saline, PA6 feeders, or undifferentiated ES cells showed no rescue. Conclusions. ES cells can differentiate, morphologically, and functionally, into RPE-like cells. Based on these findings, differentiated ES cells have the potential for the development of new therapeutic approaches for RPE-specific diseases such as certain forms of retinitis pigmentosa and macular degeneration. Nevertheless, stringent control of retinal detachment and teratoma development will be necessary before initiation of treatment trials.
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