Study on Xenotransplantation of Capsulated Porcine Choroid Plexus Cells in Rhesus PD Model

Abstract

Introduction: Parkinson's disease (PD) belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine-producing brain cells. The aim of study was to assay the potential therapeutic value of xenotransplantation of capsulated porcine choroid plexus (CP) cells to Parkinson's disease. Methods: CP cells were isolated from neonatal porcine choroid plexus, and the CP cells were encapsulated into APA CP cell capsule. Each capsule contained 2.7 CP cell clusters averagely. Nineteen adult male rhesus monkeys were made into hemi-parkinsonism by infusing MPTP into right internal carotid artery (ICA). Fifteen PD monkeys were shown typical PD features, behavior score for the rhesus was 10.93 ±3.7. The PD monkeys were randomized into three groups. Forty CP cell capsules were implanted into right caput nuclei caudate of the first group of 6 monkeys under CT guiding. Six monkeys were implanted with 40 empty capsules with same way in the second group. And the rhesus monkeys in the third group were just treated with sham surgery. Asymmetric rotation and neurological scores were assessed at 2 and 4 weeks post lesion and 2, 4, 8, 12, 16 and 24 weeks post implant. Histological analysis, anti-TH, ant-NGF and anti-NT-3 immunohistochemistry assays, were performed at termination of the study in 3 groups of rhesus. All recipients were not received any immunosuppressive protocol. Results: Twenty- four weeks after treatments, PD behavior score for the rhesus decreased by 9.3 ±1.8 points (p< 0·001) in CP cell implanted group, by 3.8 ±1.5 points in the sham group (p< 0·003) and by 4.2±1.1 in the empty capsules group. The CP cell capsules group showed a significantly improvement from baseline in behavior scores compared with the sham group and the empty capsules group. CP cell capsules were shown strong NGF and NT-3 positive staining. The Immunohistochemistry results also showed much more TH positive neurons in CP cells group compared to the sham group and the empty capsule group. Conclusion: Xenotransplantation of capsulated neonatal porcine CP cells shows positive value as potential therapy for Parkinson's disease in non-human primate model without immunosuppressive treatment.