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S.J. Van Hoffelen, M.J. Young, D.S. Sakaguchi; Retinalization of Brain-Derived Neural Progenitor Cells In Vitro . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1696.
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Purpose: The aim of this study was to investigate if brain-derived neural progenitor/stem cells could be induced to adopt retina-specific fates (retinalization) when cultured in the presence of differentiating retinal cells. We have previously shown that a small percentage of brain-derived neural progenitor cells could adopt retinal phenotypes when transplanted into the developing mammalian retina. By using a coculture system, we have investigated the role of potential molecular cues derived from developing retina on the fate of progenitor cells. Methods: Progenitor/stem cells isolated from brains of neonatal EGFP (enhanced green fluorescent protein) transgenic mice (TgN(ß-act-eGFP)04Obs) were cocultured with dissociated P1 mouse retina. Dissociated retina and progenitor cells were cultured separately as controls. Cultures were maintained for up to one month. Cultures were analyzed by immunocytochemistry using specific antibodies that have been used for identification of retinal cell types. Results: Progenitor cells were easily identified from retinal cells by their EGFP expression. After 7 days of coculturing, subpopulations of retinal neurons were found to express neurofilament, calretinin, recoverin or rhodopsin, verifying subclasses of retinal neurons. At 7 days, subpopulations of EGFP expressing cells in these cocultures were observed immunoreactive for calretinin and neurofilament antibodies, although no EGFP expressing cells were labeled with photoreceptor specific markers. However, after 21 days of coculturing, a subpopulation of EGFP expressing cells were rhodopsin immunoreactive, providing evidence for retinal specific differentiation of brain-derived neural progenitor/stem cells. No EGFP-expressing progenitor/stem cells in control cultures expressed detectable levels of rhodopsin. Conclusions: In the presence of developing retinal neurons, brain-derived neural progenitor/stem cells can be induced to express proteins characteristic of photoreceptors. Identifying and characterizing retinal-derived cues, which promote photoreceptor differentiation from neural progenitor/stem cells has important implications for treating retinal disease.
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