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H Negishi, S Kubota, M Hatano, A Mizota, E Adachi-Usami; Transplanted Embryonic Stem Cells Differentiate and Provide Substrate for Optic Nerve Regeneration in Adult Rats . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3696.
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Purpose: We have reported that optic nerve fibers regenerate into an artificial graft composed of cultured Schwann cells. The purpose of this study was to determine whether transplanted embryonic stem (ES) cells can provide a substrate into which axotomized optic nerve fibers can regenerate, and whether the ES will differentiate in the artificial milieu. Methods: ES cells were suspended in an extracellular matrix, and transferred into a 1.1 cm length permeable tube (ID=1 mm) to act as a guidance channel for the artificial graft. The graft was transplanted onto the retinal stump of a transected adult rat optic nerve (Wistar strain). The relationship between the regenerating axons and the transplanted cells was analyzed by immunohistochemistry after 3 weeks. Results: The graft remained intact and was filled with parenchymatous tissue together with neovascular tissue. Immunohistochemical analysis showed that the retinal ganglion cell axons regenerated into the artificial graft and were associated with GAP-43 and cell adhesion molecules (NCAM, L1) at 3 weeks postoperation. The transplant ES cells survived and differentiated into astrocytes (GFAP positive cells), oligodendrocyte (gal-c and 04-positive cells), and neurons (tublin-positive cells) in the graft. Conclusion: These results suggest that ES cells are an efficient substrate that can support optic nerve regeneration. The ES cells can differentiate into astrocytes, oligodendrocytes, and neurons in the artificial milieu.
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