APA Microencapsulated BCC Transplantation Into Hemiparkinsonian Monkeys: A Long-term Study On Behavior, Functional Image And Histomorphology

[Background] Up to date, neural transplant for restoring dopamine in the striatum is one of the most promising approach for treatment of Parkinson' s disease. Striatal implantation of bovine adrenal chromaffin cells could restorate function of a rat model of Parkinson' s disease. However, transplantation of adrenal medullary tissue into parkinsonian patients showed transient improvement of motor deficits. Failure of adrenal grafts was considered due to host rejection. Then, implantation of encapsulated-PC 12 has been confirmed to be able improved motor function of a animal model of Parkinson' s disease and to be protected from host rejection. We carried out study on microencapsulated BCC transplants into Hemiparkinsonian monkeys.[Objective] To investigate into remote behavioral and morphological states of microencapsulated BCC after implantation into hemiparkinsonian monkeys and explore the relationship between clinical effects and histological states.[Material and Methods] 9 monkeys were rendered hemiparkinsonism with an intracarotid injection of MPTP. 6 monkeys received implants of microencapsulated BCCs into the caudate nucleus and putamen, 2 monkeys and 1 monkey received identical implants of unencapsulated BCCs and emptyencapsulates respectively, served as a control. After transplantation, their behavior were recorded and trials of Apo-induced turning performed regularly. One monkey with microencapsulated BCCs was investigated by PET. 8 monkeys were examined by routine neuropathological methods and immunohistochemistry by using antibodies such as TH, GFAP, CDS, CD20, CD68 at 14-28 months posttransplantation.[Results] 9 monkeys presented hemiparkinsonism after MPTP injection. 8 of them were observed that amount of cells on right side substantia nigras reduced by 80% or above as compared with those of the left side. After transplantation, restoration of function in microencapsulated BCC group and unencapsulated BCC were observed, no improvement of function with empty encapsulates were found. Furthermore, microencapsulated BCC have longer lasting times of improvement of parkinsonian symptoms. Among them, recovery of function in one monkey reach to near normal levels for up to 28 months. In contrast to this, improvement of unencapsulated BCC group lasts only for 1-2 month. Functional image on brain PET of one monkey with microencapsulated BCC showed right striatum D2 receptor activity is higher than that on left striatum at 48 months posttransplantation. On histological examination, a large number of microencapsulates in 2 monkeys with microencapsulated BCC implants were founded, within microencapsulates, there are a few viable BCC. Density of Th-ir fibers in the striatum near microencapsulates is higher than that in the left striatum. Microencapsulates in 3 monkeys with microencapsulated BCCs were not founded and implants sites were refilled with reactive gliosis and immunoreactive cells; no viable BCC were observed. No survival of BCC in unencapsulated BCC groupwere observed. There are modest immune response in implant site of monkeys with intact microencapsulates, prominent immunological cells infiltration occurred in cases with broken microencapsulates. No distinct immune response occurred in monkey with empty microencapsulates implants.[Conclusion] Microencapsulated BCC implantation into hemiparkinsonian monkey could remain long-term time, and could be found a viable BCC in case of intact microencapsulates. Histological response of the host brain surrounding the intact encapsulate is minimal. Degrees and lasting time of recovery of function in hemiparkinsonian monkey are related to histological states of microencapsulated BCC in the brain and recovery of dopaminergic fibers.