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K. Warfvinge, P.H. Schwartz, J.F. Kiilgaard, H. Nethercott, E. Scherfig, M.J. Young, H. Klassen; Transplantation of Human Neural Progenitor Cells to Pig Subretinal Space . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3228.
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Purpose: To clinically and histologically evaluate the effect on the host, and to investigate immunocytochemically survival, integration and differentiation of characterized human neural progenitor cells after subretinal transplantation to adult normal pigs. Methods: Neural progenitor cells (NPCs) were obtained postmortem from a 25 week premature infant. Forebrain tissue was enzymatically dissociated and plated in medium containing EGF, bFGF, and PDGF. After repeated passaging, the resulting cell population was characterized in terms of marker expression. NPCs were grafted to the pig subretinal space after laser injury and followed with fundus photos until sacrifice at 10–30 days. Histological evaluation included H&E and immunocytochemistry, including anti–human antibodies. Results: The post–op examinations showed brighter areas in the regions of transplantation. Retinal vessels seemed normal and there were no signs of exudation, bleeding or subretinal elevation. NPCs survived up to 14 days post–transplantation. After 4 weeks (n=1), no surviving cells were found. H&E showed a mild retinal vasculitis, depigmentation of the RPE, and a marked increase in mononuclear inflammatory cells in the choroid adjacent to the site of transplantation. Immunocytochemically, human–specific antibodies revealed human cells in the subretinal space, but differentiation into retinal specific cells was not seen. Conclusions: Human NPCs survive xenografting to an immune privileged site, albeit for a limited time. While this period might be extended using immunosuppressive agents, allogeneic NPCs are likely to be better tolerated, and therefore more useful for studying cell replacement strategies in large animal models.
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