en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <strong>Introduction: </strong>The induction of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) toward dopaminergic neurons is a major challenge in tissue engineering and experimental and clinical treatments of various neurodegenerative diseases, including Parkinson disease. This study aims to differentiate HUC-MSCs into dopaminergic neuron-like cells.<br> <strong>Methods:</strong> Following the isolation and characterization of HUC-MSCs, they were transferred to Matrigel-coated plates and incubated with a cocktail of dopaminergic neuronal differentiation factors. The capacity of differentiation into dopaminergic neuron-like cells in 2-dimensional culture and on Matrigel was assessed by real-time polymerase chain reaction, immunocytochemistry, and high-performance liquid chromatography.<br> <strong>Results:</strong> Our results showed that dopaminergic neuronal markers&rsquo; transcript and protein levels were significantly increased on the Matrigel differentiated cells compared to 2D culture plates.<br> <strong>Conclusion:</strong> Overall, the results of this study suggest that HUC-MSCs can successfully differentiate toward dopaminergic neuron-like cells on Matrigel, having great potential for the treatment of dopaminergic neuron-related diseases. Differentiation, Dopaminergic neurons, Human umbilical cord mesenchymal stem cells, In vitro 625 636 http://bcn.iums.ac.ir/browse.php?a_code=A-10-973-3&slc_lang=en&sid=1 Ardeshir Moayeri 13700319475328460043024 13700319475328460043024 No Department of Anatomy, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran. Rafieh Alizadeh moayeri46@yahoo.com 13700319475328460043025 13700319475328460043025 No ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Hatef Ghasemi Hamidabadi hatefdr@gmail.com 13700319475328460043026 13700319475328460043026 Yes Department of Anatomy & Cell Biology, Immunogenetic Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Maryam Nazm Bojnordi 13700319475328460043027 13700319475328460043027 No Department of Anatomy & Cell Biology, Immunogenetic Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Ali Niapour 13700319475328460043028 13700319475328460043028 No Department of Anatomical Sciences, Research Laboratory for Embryology and Stem Cells, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran. Azim Hedayatpour 13700319475328460043029 13700319475328460043029 No Department of Anatomy, School of Medicine, University of Tehran, Tehran, Iran. Marzieh Darvishi 13700319475328460043030 13700319475328460043030 No Department of Anatomy, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran. Fatemeh Heidari 13700319475328460043031 13700319475328460043031 No Department of Anatomy, School of Medicine, Qom University of Medical Sciences, Qom, Iran. Maryam Soleimani 13700319475328460043032 13700319475328460043032 No Department of Basic Sciences, School of Rehabilitation Sciences, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. Leila Elyasi 13700319475328460043033 13700319475328460043033 No Department of Anatomy, Neuroscience Research Center, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.