摘要BACKGROUND: Human amniotic epithelial cells (HAECs) can differentiate into neurons, astrocytes,and oligodendrocytes. They biologically secrete many active neurotrophins and have the capacity to metabolize dopamine enzymes. These features underlie a theoretical basis for the treatment of Parkinson's disease (PD).OBJECTIVE: To investigate the survival and differentiation of transplanted HAECs in the lateral ventricle of PD model rats, and to explore its effect on circling behavior, as well as levels of dopamine (DA), the metabolite homovanillic acid, dihydroxyphenyl acetic acid,5-hydroxyindoleacetic acid, and 5-hydroxytryptamine in the striatum.DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, and Shanghai Celstar Institute of Biotechnology from May 2007 to December 2008.MATERIALS: HAECs were derived from the placental chorion following caesarean delivery at the Shanghai International Maternal and Child Health Hospital. 6-hydroxydopamine (6-OHDA), and mouse anti-human Vimentin monoclonal antibody were purchased from Sigma, USA; mouse anti-human nestin and tyrosine hydroxylase (TH) monoclonal antibodies were purchased from Chemicon, USA.METHODS: A total of 114 healthy, adult, Sprague Dawley rats were randomly assigned to two groups: PD model [n = 90, stereotactic microinjection of 2 μL 6-OHDA (3.5 μg/μL) into the striatum] and control (n = 24, no treatment). The 51 successful PD model rats were randomly divided into 3 subgroups (n= 17): HAEC, PBS, and model. The HAEC and PBS groups were respectively injected with 10 μL PBS solution containing 1×10~5/mL HAECs or 10 μL PBS into the lateral ventricle. The model group was not treated.MAIN OUTCOME MEASURES: TH protein expression in the striatum was evaluated by immunohistochemistry 5 weeks after HAEC transplantation. At 10 weeks, HAEC survival in the lateral ventricle was investigated by immunofluorescent staining; differentiation of HAECs in the lateral and third ventricles was examined by TH immunohistochemistry; concentrations of DA,homovanillic acid, dihydroxyphenyl acetic acid, 5-hydroxyindoleacetic acid, and 5-hydroxytryptamine in the striatum, as well as DA concentration in the cerebrospinal fluid, were measured with high-performance liquid chromatography-electrochemical detection. Circling behavior of PD model rats was consecutively observed for 10 weeks following intraperitoneal injection of amphetamine 1 week after successful model establishment.RESULTS: In the HAEC group, the number of TH-positive cells significantly increased in the striatum, and circling behavior significantly decreased, compared with the PBS and model groups (P< 0.01). In addition, monoamine concentrations in the striatum, as well as DA concentrations in the cerebrospinal fluid, significantly increased, compared with the PBS group (P< 0.05-0.01).Moreover, a large number of nestin-, vimentin-, and TH-positive cells were observed in the lateral and third ventricles following HAEC injection.CONCLUSION: HAECs survived for 10 weeks with no overgrowth following transplantation into the lateral ventricle of PD model rats. Moreover, the cells differentiated into dopaminergic neurons, which increased DA secretion. HAEC transplantation improved cycling behavior in PD model rats.