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E. Banin, A. Obolensky, M. Idelson, T. Ben–Hur, B. Reubinoff; Retinal Differentiation of Neural PrecursorsDerived From Human Embryonic Stem Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5749.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the potential of human embryonic stem (hES) cell–derived neural progenitors to survive, integrate and differentiate into retinal cells following in–vivo intraocular transplantation in rodent eyes.
Spheres enriched for neural progenitors (NPs) were derived from hES cells cultured on mitotically inactivated feeders in the presence of the BMP antagonist noggin. Immunocytochemical methods and RT–PCR were used to analyze the expression of neural, glial and ocular markers by cells within the spheres after 4 weeks of cultivation. Between 60,000–100,000 NPs, or saline, were injected into the vitreal and/or sub–retinal space of adult and newborn Sabra rat eyes. Survival of the transplanted cells, their migration and differentiation were assessed by histomorphology and immunohistochemistry at sequential time points up to 4 months after injection.
Human ES cell–derived NPs expressed transcripts of key regulatory genes of anterior brain and retina development including Pax6, LHX2, CHX10, Six6, Six3, CRX, NRL, recoverin and blue cone opsin. Following in–vivo intraocular transplantation, the grafts survived for 16 weeks. Transplanted cells migrated to large distances from the main graft and integrated in the host retina. As early as 2 weeks post–injection, but more often at 1–4 months post–injection, engrafted human cells expressing rhodopsin, blue cone opsin, and NRL were observed in sub–retinal grafts. These photoreceptoral markers were not expressed by hES cells that were engrafted into the vitreous and inner retina.
Human ES cell–derived NPs have the developmental potential to differentiate into retinal cells. The microenvironment of the sub–retinal space promotes their differentiation into cells expressing photoreceptor–specific markers. This may be a first step towards the future use of hES cells for therapeutic transplantation in retinal degenerations.
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