Transplantation of Human Neural Progenitor Cells to the Vitreous Cavity of the Royal College of Surgeons Rat

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Abstract
Human neural progenitor cells, originally isolated from prenatal donor tissue at 17 weeks of development, were cultured as neurospheres and transplanted to the vitreous cavity of dystrophic Royal College of Surgeons rats with, or without, cyclosporin A immunosuppression. Donor cells were either unlabeled or prelabeled, the latter utilizing incubation with BrdU or adenoviral modification to express green fluorescent protein. Recipients of various ages were examined at 1, 2, and 4 weeks postgrafting. Transplanted human neural progenitor cells survived in the host vitreous for at least 4 weeks and maintained expression of green fluorescent protein for at least 2 weeks. After 2 weeks in vivo, grafted cells differentiated morphologically, coincident with expression of the neuronal marker MAP, indicating mature neuronal differentiation. The extensive intraretinal migration previously shown using rat progenitor cells in the Royal College of Surgeons rat model was not seen in this experiment, suggesting that high levels of neuronal migration may depend at least in part upon species-specific molecular cues. Human neural progenitor cells represent a renewable source of multipotent human cells capable of in vivo neuronal development and a potential means of delivering therapeutic factors intraocularly. Human neural progenitor cells therefore provide a useful tool for studies of neural development and differentiation in the dystrophic eye.