title: Creatine Enhances Transdifferentiation of Bone Marrow Stromal Cell-Derived Neural Stem Cell Into GABAergic Neuron-Like Cells Characterized With Differential Gene Expression.
abstract: Creatine was reported to induce bone marrow stromal cells (BMSC) into GABAergic neuron-like cells (GNLC). In a previous study, creatine was used as a single inducer for BMSC into GNLC with low yield. In this study, BMSC-derived neurospheres (NS) have been used in generating GABAergic phenotype. The BMSC were isolated from adult rats and used in generating neurospheres and used for producing neural stem cells (NSC). A combination of all-trans-retinoic acid (RA), the ciliary neurotrophic factor (CNTF), and creatine was used in order to improve the yield of GNLC. We also used other protocols for the transdifferentiation including RA alone; RA and creatine; RA and CNTF; and RA, CNTF, and creatine. The BMSC, NSC, and GNLC were characterized by specific markers. The activity of the GNLC was evaluated using FM1-43. The isolated BMSC expressed Oct4, fibronectin, and CD44. The NS were immunoreactive to nestin and SOX2, the NSC were immunoreactive to nestin, NF68 and NF160, while the GNLC were immunoreactive to GAD1/2, VGAT, GABA, and synaptophysin. Oct4 and c-MYC, pluripotency genes, were expressed in the BMSC, while SOX2 and c-MYC were expressed in the NSC. The activity of GNLC indicates that the synaptic vesicles were released upon stimulation. The conclusion is that the combination of RA, CNTF, and creatine induced differentiation of neurosphere-derived NSC into GNLC within 1 week. This protocol gives higher yield than the other protocols used in this study. The mechanism of induction was clearly associated with several differential pluripotent genes.
authors.affiliation: Department of Anatomical Sciences, School of Medical Sciences, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Darabi
authors.affiliation: Department of Anatomical Sciences, School of Medical Sciences, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran. takialtr@modares.ac.ir.|Shefa Neurosciences Research Center, Khatam Al-Anbia Hospital, Tehran, Iran. takialtr@modares.ac.ir.
authors.forename: Taki
authors.initials: T
authors.lastname: Tiraihi
authors.affiliation: Department of Anatomy, Shahed University, Tehran, Iran.
authors.forename: AliReza
authors.initials: A
authors.lastname: Delshad
authors.affiliation: Department of Genetics, Faculty of Basic Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Sadeghizadeh
authors.affiliation: Shefa Neurosciences Research Center, Khatam Al-Anbia Hospital, Tehran, Iran.
authors.forename: Taher
authors.initials: T
authors.lastname: Taheri
authors.affiliation: Middle Euphrates Neuroscience Center-Kufa College of Medicine, Annajaf, Iraq.
authors.forename: Hayder K
authors.initials: HK
authors.lastname: Hassoun
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D054338:Cell Transdifferentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003401:Creatine / Q000494:pharmacology*; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003401:Creatine
keywords: BMSC; GABAergic neuron; Induction; Neurospheres; Pluripotency gene