Transplantation of EGF-responsive neurospheres from GFP transgenic mice into the eyes of rd mice

The isolation of stem cells from various regions of the central nervous system has raised the possibility of using them as a donor cell source for cell transplantation, where they offer great promise for repair of the diseased brain, spinal cord, and retina. Here, we have studied the migration, integration, and differentiation of EGF-responsive neurospheres isolated from the brains of green fluorescent protein transgenic mice and transplanted into the eyes of mature rd mice, a model of retinitis pigmentosa. While grafts of freshly isolated postnatal day 8 retina expressed many markers characteristic of mature retina (e.g. rhodopsin, protein kinase C), very few of the grafted cells migrated into host retina. EGF-responsive neurospheres, conversely, readily migrated into and integrated with the remaining host retina, but showed a very limited ability to differentiate into mature retinal neurons. While the progenitor cells used here show remarkable ability to integrate with host retina and develop some attributes of retinal cells, the failure to fully differentiate into retinal cells suggests that they already express some level of terminal commitment that precludes using them to replace lost photoreceptors.