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Functional dopaminergic neurons derived from human chorionic mesenchymal stem cells ameliorate striatal atrophy and improve behavioral deficits in Parkinsonian rat model
Authors:Vahid Ebrahimi  Mahdi Eskandarian Boroujeni  Abbas Aliaghaei  Mohammad Amin Abdollahifar  Abbas Piryaei  Hossein Haghir  Yousef Sadeghi
Affiliation:1. Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Department of Stem Cells and Regenerative Medicine, Faculty of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran;3. Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;4. Department of Anatomy, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Medical Genetic Research Center (MGRC), Mashhad University of Medical Sciences, Mashhad, Iran

Abstract:Human chorionic mesenchymal stem cells (HCMSCs) have been recognized as a desirable choice for cell therapy in neurological disorders such as Parkinson's disease (PD). Due to invaluable features of HCMSCs including their immunomodulatory and immunosuppressive properties, easily accessible and less differentiated compared to other types of MSCs, HCMSCs provide a great hope for regenerative medicine. Thus, the purpose of this study was to determine the in vitro and in vivo efficacy of HCMSCs-derived dopaminergic (DA) neuron-like cells with regard to PD. Initially, HCMSCs were isolated and underwent a 2-week DA differentiation, followed by in vitro assessments, using quantitative real-time polymerase chain reaction, immunocytochemistry, patch clamp recording, and high-performance liquid chromatography. In addition, the effects of implanted HCMSCs-derived DA neuron-like cells on the motor coordination along with stereological alterations in the striatum of rat models of PD were investigated. Our results showed that under neuronal induction, HCMSCs revealed neuron-like morphology, and expressed neuronal and DA-specific genes, together with DA release. Furthermore, transplantation of HCMSCs-derived DA neurons into the striatum of rat models of PD, augmented performance. Besides, it prevented reduction of striatal volume, dendritic length, and the total number of neurons, coupled with a diminished level of cleaved caspase-3. Altogether, these findings suggest that HCMSCs could be considered as an attractive strategy for cell-based therapies in PD.
Keywords:chorion  dopaminergic neuron  mesenchymal stem cells  neurodifferentiation  Parkinson's disease  stereology
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