title: Differentiation of Wharton's Jelly-Derived Mesenchymal Stem Cells into Motor Neuron-Like Cells on Three-Dimensional Collagen-Grafted Nanofibers.
abstract: Cell transplantation strategies have provided potential therapeutic approaches for treatment of neurodegenerative diseases. Mesenchymal stem cells from Wharton's jelly (WJMSCs) are abundant and available adult stem cells with low immunological incompatibility, which could be considered for cell replacement therapy in the future. However, MSC transplantation without any induction or support material causes poor control of cell viability and differentiation. In this study, we investigated the effect of the nanoscaffolds on WJMSCs differentiation into motor neuronal lineages in the presence of retinoic acid (RA) and sonic hedgehog (Shh). Surface properties of scaffolds have been shown to significantly influence cell behaviors such as adhesion, proliferation, and differentiation. Therefore, polycaprolactone (PCL) nanofibers were constructed via electrospinning, surface modified by plasma treatment, and grafted by collagen. Characterization of the scaffolds by means of ATR-FTIR, contact angel, and Bradford proved grafting of the collagen on the surface of the scaffolds. WJMSCs were seeded on nanofibrous and tissue culture plate (TCP) and viability of WJMSCs were measured by MTT assay and then induced to differentiate into motor neuron-like cells for 15 days. Differentiated cells were evaluated morphologically, and real-time PCR and immunocytochemistry methods were done to evaluate expression of motor neuron-like cell markers in mRNA and protein levels. Our results showed that obtained cells could express motor neuron biomarkers at both RNA and protein levels, but the survival and differentiation of WJMSCs into motor neuron-like cells on the PCL/collagen scaffold were higher than cultured cells in the TCP and PCL groups. Taken together, WJMSCs are an attractive stem cell source for inducing into motor neurons in vitro especially when grown on nanostructural scaffolds and PCL/collagen scaffolds can provide a suitable, three-dimensional situation for neuronal survival and differentiation that suggest their potential application towards nerve regeneration.
authors.affiliation: Department of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Bagher
authors.affiliation: Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Azami
authors.affiliation: Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.|Brain and Spinal Injury Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Ebrahimi-Barough
authors.affiliation: Polymer Engineering Faculty, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Mirzadeh
authors.affiliation: Biomedical Engineering Faculty, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Solouk
authors.affiliation: Department of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.|Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.|Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansooreh
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.|Brain and Spinal Injury Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Ai
authors.affiliation: Tissue Engineering Division, Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Nourani
authors.affiliation: Department of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. joghataei.mt@iums.ac.ir.|Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. joghataei.mt@iums.ac.ir.|Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. joghataei.mt@iums.ac.ir.
authors.forename: Mohammad Taghi
authors.initials: MT
authors.lastname: Joghataei
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D011091:Polyesters / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D054457:Tissue Scaffolds / Q000737:chemistry; D059631:Wharton Jelly / Q000166:cytology*
chemical_list: D011091:Polyesters; D012997:Solvents; C016240:polycaprolactone; D003094:Collagen
keywords: Motor neuron differentiation; Nanofibrous scaffolds; Wharton’s Jelly-derived mesenchymal stem cell