ABSTRACT
BACKGROUND AND PURPOSE: To assess the clinical effect of transplantation of human retinal pigment epithelial (hRPE) cells into the unilateral postcommissural putamen for treatment for Parkinson disease (PD). METHODS AND RESULTS: Cells from postmortem human eye tissue (10-20 weeks of gestation) were cultured in vitro. Cells from -generation passage were implanted in PD postcommissural putamen with stereotactic operation in 12 patients with PD. All patients tolerated surgery well, and no major adverse events occurred. Eleven patients showed improvement in the primary outcome measure at 3 months post-treatment, particularly the Unified Parkinson's Disease Rating Scale-M score in the off state. Response reached a peak at 12 months and declined during the next 24 months. At the 36-month endpoint, there were eight patients who felt better than at baseline. Positron emission tomography (PET) showed a trend with increased dopamine (DA) release during the first 6 months. CONCLUSION: Human retinal pigment epithelial cells have the characteristics of neural progenitor cells and can be induced to differentiate into DA neurons. The results of this clinical trial suggest that the treatment of transplanted hRPE cells could improve symptoms of PD. These cells might serve as a useful source of DA neurons for neural graft in the treatment for PD.
Subject(s)
Neural Stem Cells/transplantation , Neurons/transplantation , Parkinson Disease/surgery , Retinal Pigment Epithelium/cytology , Aged , Aged, 80 and over , Antigens, CD/genetics , Antigens, CD/metabolism , Bucladesine/pharmacology , Carbon Isotopes/pharmacokinetics , Cell Differentiation/drug effects , Cells, Cultured , Cocaine/analogs & derivatives , Cocaine/pharmacokinetics , Dopamine Uptake Inhibitors/pharmacokinetics , Female , Fetus , Flow Cytometry , Growth Substances/pharmacology , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Neural Stem Cells/physiology , Neurons/physiology , Parkinson Disease/diagnostic imaging , Pituitary Adenylate Cyclase-Activating Polypeptide/pharmacology , Positron-Emission Tomography , Severity of Illness Index , Time Factors , Treatment Outcome , Tretinoin/pharmacologyABSTRACT
We studied serum proteomic profiling in patients with graft versus host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) by two-dimensional gel electrophoresis (2-DE) and mass spectrometry analysis. The expression of a group of proteins, haptoglobin (Hp), alpha-1-antitrypsin, apolipoprotein A-IV, serum paraoxonase and Zn-alpha-glycoprotein were increased and the proteins, clusterin precursor, alpha-2-macroglobulin, serum amyloid protein precursor, sex hormone-binding globulin, serotransferrin and complement C4 were decreased in patients with extensive chronic GVHD (cGVHD). Serum haptoglobin (Hp) levels in patients with cGVHD were demonstrated to be statistically higher than in patients without cGVHD and normal controls (p < 0.01). We used immunoblotting and PCR in combination with 2-DE gel image analysis to determine Hp polymorphisms in 25 allo-HCT patients and 16 normal donors. The results demonstrate that patients with cGVHD had a higher incidence of HP 2-2 phenotype (43.8%), in comparison to the patients without cGVHD (0%) and normal donors (18.7%), suggesting the possibility that specific Hp polymorphism may play a role in the development of cGVHD after allo-HCT. In this study, quantitative serum Hp levels were shown to be related to cGVHD development. Further, the data suggest the possibility that specific Hp polymorphisms may be associated with cGVHD development and warrant further investigation.
