title: Tetracycline-regulated expression of OLIG2 gene in human dental pulp stem cells lead to mouse sciatic nerve regeneration upon transplantation.
abstract: Numerous studies have indicated dental pulp stem cells (DPSCs) potency to differentiate into several types of cell lineages. Oligodendrocyte lineage transcription factor 2 (OLIG2) plays an important role in the oligodendrogenic pathway. In this study, a tetracycline (Tet)-inducible system expressing OLIG2 gene was transfected into human DPSCs to direct their differentiation toward oligodendrocyte progenitor cells (OPCs). Following induction, the expression of stage-specific markers was studied by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR), immunocytochemistry and western blotting. In the following, the cells were transplanted into the mouse model of local sciatic demyelination damage by lysolecithin. Recovery of lysolecithin-induced lesions in sciatic nerve was studied by treadmill exercise, von Frey filament test and hind paw withdrawal in response to a thermal stimulus. Improvement of behavioral symptoms was efficiently observed from the second week to the sixth week post-transplantation. Our findings showed that exogenous expression of the OLIG2 gene by a Tet-regulated system could be used as an efficient way to induce the differentiation of DPSCs into functional oligodendrocytes. Meanwhile, the DPSC-derived OPCs have relevant therapeutic potential in the animal model of sciatic nerve injury and therefore might represent a valuable tool for stem cell-based therapy in inflammatory and degenerative diseases of the peripheral and central nervous systems (CNSs).
authors.affiliation: National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Electronic address: nahid.askari@yahoo.com.
authors.forename: N
authors.initials: N
authors.lastname: Askari
authors.affiliation: Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran. Electronic address: m.yaghoobi@kgut.ac.ir.
authors.forename: M M
authors.initials: MM
authors.lastname: Yaghoobi
authors.affiliation: National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Electronic address: shamsa_m_2000@yahoo.com.
authors.forename: M
authors.initials: M
authors.lastname: Shamsara
authors.affiliation: Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran. Electronic address: Semahani@yahoo.com.
authors.forename: S
authors.initials: S
authors.lastname: Esmaeili-Mahani
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008244:Lysophosphatidylcholines / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D020426:Sciatic Neuropathy / Q000139:chemically induced / Q000503:physiopathology / Q000601:surgery; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013752:Tetracycline / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D008244:Lysophosphatidylcholines; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D011500:Protein Synthesis Inhibitors; D013752:Tetracycline; C512773:Olig2 protein, mouse
keywords: OLIG2 transcription factor; Tet-regulated system; dental pulp stem cells; oligodendrocyte progenitor cells