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Creatine Enhances Transdifferentiation of Bone Marrow Stromal Cell-Derived Neural Stem Cell Into GABAergic Neuron-Like Cells Characterized With Differential Gene Expression

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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.

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Acknowledgments

The project was funded by Shefa Neurosciences Research Center at Khatam Al-Anbia Hospital, Tehran, Iran (Grant # 86-N-105). We are also grateful for the support of the Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. We express deep gratitude to Mrs. H. AliAkbar for editing the manuscript.

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Authors and Affiliations

  1. Department of Anatomical Sciences, School of Medical Sciences, Tarbiat Modares University, P.O. Box 14155-4838, Tehran, Iran

    Shahram Darabi & Taki Tiraihi

  2. Shefa Neurosciences Research Center, Khatam Al-Anbia Hospital, Tehran, Iran

    Taki Tiraihi & Taher Taheri

  3. Department of Anatomy, Shahed University, Tehran, Iran

    AliReza Delshad

  4. Department of Genetics, Faculty of Basic Sciences, Tarbiat Modares University, Tehran, Iran

    Majid Sadeghizadeh

  5. Middle Euphrates Neuroscience Center-Kufa College of Medicine, Annajaf, Iraq

    Hayder K. Hassoun

Authors
  1. Shahram Darabi
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  2. Taki Tiraihi
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  3. AliReza Delshad
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  4. Majid Sadeghizadeh
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  5. Taher Taheri
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  6. Hayder K. Hassoun
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Corresponding author

Correspondence to Taki Tiraihi.

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Darabi, S., Tiraihi, T., Delshad, A. et al. Creatine Enhances Transdifferentiation of Bone Marrow Stromal Cell-Derived Neural Stem Cell Into GABAergic Neuron-Like Cells Characterized With Differential Gene Expression. Mol Neurobiol 54, 1978–1991 (2017). https://doi.org/10.1007/s12035-016-9782-9

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  • DOI: https://doi.org/10.1007/s12035-016-9782-9

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