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DS Sakaguchi, SJ Van Hoffelen, MA Shatos, MJ Young; Morphological Integration and Differeniation of Murine Brain Stem Cells Transplanted Into the Developing Mammalian Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):920.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the influence of the age of the host environment on the fate of murine brain stem cells (mBSCs) following transplantation into developing and mature mammalian eyes. Methods: Progenitor cells were isolated from newborn brains of eGFP (enhanced green fluorescent protein), transgenic mice (TgN(ß-act-eGFP)04Obs). Brazilian opossums, Monodelphis domestica, served as the hosts for these transplant studies. Monodelphis is a small, pouchless marsupial that breeds well under laboratory conditions and whose young are born in an extremely immature, fetal-like, state. Animals received intravitreal transplants of mBSCs, with host ages ranging from 5 days postnatal (5 PN) to adult. Animals were allowed to survive for up to 4 weeks post transplant at which time the eyes were prepared for immunohistochemical analysis. Results: Transplanted cells were easily identified by fluorescence of the eGFP (GFP+). Transplanted mBSCs survived and differentiated in vivo and extensive morphological integration was observed within the host retinas. GFP+ cells often displayed morphologies characteristic of ganglion cells, amacrine cells, bipolar cells and horizontal cells. Transplanted cells generally respected the architectural organization of the host eyes. GFP+ somata were situated in nuclear layers, and their processes ramified throughout the inner (IPL) and outer (OPL) plexiform layers. Furthermore, in some cases, GFP+ neurites were confined to specific sublamina within the IPL. The greatest morphological integration and differentiation was observed in the youngest host eyes, with very little integration observed in the mature eyes. Antibody markers were used to evaluate whether grafted cells adopted neural phenotypes. Transplanted mBSCs incorporated within the inner retina (and vitreous) often co-expressed the neuronal marker MAP2. Subpopulations of GFP+ cells incorporated within the INL were found to express calretinin, a marker associated with some retinal interneurons. Conclusions: mBSCs survived and differentiated after xenotransplantation into the Brazilian opossum eye. The younger the host environment, the greater the morphological integration of transplanted mBSCs. These results suggest that transplanted mBSCs may be capable of responding to local cues in the microenvironment that promotes their differentiation and integration.
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