Xenotransplantation of microencapsulated bovine chromaffin cells into the brain of hemiparkinsonian monkeys

AIM: To observe the effects of xenotransplantation of microencapsulated bovine chromaffin cells (BCCs) on behavior of hemiparkinsonian monkeys, survival state of xenografts and changes in contents of monoamine neurotransmitters as well as activities of dopamine D2 receptors in neostriatum. METHODS: The experiment was conducted in the Institute of Geriatrics, General Hospital of Chinese PLA from January 1999 to June 2003. ① The hemiparkinsonian models of monkey (n=9) were induced by right intracarotid injection of methyl-phenyl-tetrahydropyridine (MPTP), and then randomly divided into microencapsulated BCC group (n=6), BCC group (n=2) and empty microcapsule group (n=1).②BCCs were obtained and packed with alginate-polylysine-alginate (APA). BCCs of microencapsulation and non-microencapsulation and empty microcapsule were implanted respectively into the right caudate nucleus (RCN) and dorsal caudate putamen (DCPU) of hemiparkinsonian monkeys in the microencapsulated BCC group, BCC group and empty microcapsule group.③The post-grafted behavior, histological states of xenografts at 14 months and 28 months after transplantation in 3 groups were observed, and post-grafted contents of monoamine neurotransmitters at 2 months and 7 months after transplantation and the activity of dopamine D2 receptors in neostriatum at 48 months after transplantation were studied in the microencapsulated BCC group. RESULTS: ①The hemiparkinsonian symptoms of left upper limbs in monkeys of the encapsulated BCC group (n=6) and BCC group (n=2) were obviously increased at one week after transplantation. The amelioration in encapsulated BCC group lasted for 7-48 months, and that in the BCC group was 1-2 months, whereas no change was observed in the empty microcapsule group (n=1).②The microencapsulated BCCs were still alive in hemiparkinsonian monkey's brain on the 28th month.③At 2 and 7 months after transplantation of encapsulated BCCs, the DCPU of right side, level of dopamine in extracellular fluid of caudate nucleus, 3,4-dihydroxybenzene and homovanillic acid increased markedly than those before transplantation (P < 0.05), however, those were still lower than levels of the left side.④The activity of D2 receptor in microencapsulated BCCs at 48 months of post-transplantation was higher than that in the opposite side. CONCLUSION: The results indicate that the xenotransplantation of microencapsulated BCCs can longly survive in the hemiparkinsonian monkeys, which produce dopamine and can ameliorate the abnormal behavior of hemiparkinsonian monkeys.