Transplantation of Xenogeneic Retinal Stem Cells to Pig Subretinal Space

Abstract

Abstract: : Purpose: Histologic evaluation of the host response to retinal stem cells from transgenic mice following transplantation to the subretinal space of pigs. Methods: A total of 14 domestic pigs aged 3 month were used. Retinal burns were created at the time of surgery in 7 animals with a diode laser. All pigs underwent a three-port vitrectomy and subretinal transplantation of retinal stem cells from transgenic GFP-mice. Cells were delivered as a single cell suspension or as neurospheres (~1 x 106 cells). No immunosuppression was used. The recipients were allowed to survive for 1,2 or 5 weeks. Fundus photos were obtained just prior to enucleation. Eyes were fixed and processed for cryo-sectioning. Histopathological evaluation was performed on HE stained sections. Results: At 1 week, HE staining 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. Larger choroidal infiltrates were seen at 2 and 5 weeks, and tended to localize into distinct foci, but did not differ between laser- and untreated groups. Donor cells could be detected at 1 and 2 weeks, but no grafted cells were found at 5 weeks. Conclusions: Xenogeneic retinal stem cells grafted to the porcine subretinal space survive for 2 weeks, but induce a marked mononuclear choroidal infiltrate at the transplantation site, suggestive of graft rejection. The basis of this response remains unclear. The use of allogeneic porcine retinal stem cells may avoid this complication.

Keywords: transplantation • microscopy: light/fluorescence/immunohistochem • animal model