Retinal integration of grafts of brain-derived precursor cell lines implanted subretinally into adult, normal rats

The ability of in vitro-expanded neural precursor cells or cell lines to di fferentiate following transplantation has significant implications for curr ent research on central nervous system repair. Recently, interest has been focussed on grafts of such neural precursors implanted also into the eye or retina. Here, we demonstrate with a non-traumatizing subretinal transplant ation method, that grafts of the two immortalized brain-derived cell lines C 17-2 (from postnatal mouse cerebellum) and RN33B (from the embryonic rat medullary raphe) survive for at least up to four weeks, after implantation into the adult normal rat retina. For both cell lines, implanted cells grad ually integrate into all major retinal cell layers, including the retinal p igment epithelium, and judged by the morphology differentiate into both gli al- and neuronlike cells, as shown by thymidine autoradiography, mouse-spec ific in situ hybridization, and using immunohistochemistry to detect the re porter gene Lac Z. Our results suggest that these and other similar neural cell lines could be very useful in the continuos experiments in models of r etinal disorders to further assess both the cell replacement and ex vivo ge ne therapy approaches. (C) 2001 Academic Press.