Hypoxic Preconditioning Increases the Neuroprotective Effects of Mesenchymal Stem Cells in a Rat Model of Spinal Cord Injury

نویسندگان

  • Takeshi Imura
  • Mayumi Tomiyasu
  • Naofumi Otsuru
  • Kei Nakagawa
  • Takashi Otsuka
  • Shinya Takahashi
  • Masaaki Takeda
  • Louis Yuge
چکیده

The functional deficit caused by Spinal Cord Injury (SCI) is clinically incurable and current treatments have limited effects. Previous studies have suggested that cell-based therapy using Mesenchymal Stem Cells (MSCs) pre-treated with drugs or gene transfection have possible therapeutic effects. Hypoxic preconditioning is one of the most likely treatments of cell-based therapy without altering genes; however, few reports are available about Hypoxia-Preconditioned MSCs (H-MSC) transplantation for SCI. Here we demonstrate the therapeutic potential of H-MSC transplantation using SCI model rats. H-MSC expressed significantly higher mRNA levels of vascular endothelial growth factor-1 and carbonic anhydrase IX, hypoxia inducible genes. H-MSC transplantation resulted in remarkable functional improvement in the SCI model rats compared to no transplantation. Expression of brainderived neurotrophic factor and the autophagy-associated marker beclin1 mRNA was significantly upregulated in rat spinal cord that underwent H-MSC transplantation. Furthermore, conditioned medium of the H-MSC significantly prevented cell death of NG108-15 cells exposed to oxidative or inflammatory stress. These results suggest that hypoxia preconditioning is an effective strategy for SCI in cell-based therapy using MSCs. Hypoxic Preconditioning Increases the Neuroprotective Effects of Mesenchymal Stem Cells in a Rat Model of Spinal Cord Injury Takeshi Imura1, Mayumi Tomiyasu1, Naofumi Otsuru1, Kei Nakagawa1, Takashi Otsuka1, Shinya Takahashi2, Masaaki Takeda3, Looniva Shrestha1, Yumi Kawahara4, Takahiro Fukazawa5, Taijiro Sueda2, Keiji Tanimoto6 and Louis Yuge1,4* 1Bio-Environmental Adaptation Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, Japan 2Department of Cardiovascular Surgery, Hiroshima University Hospital, Japan 3Department of Neurosurgery, Graduate School of Biomedical & Health Sciences, Hiroshima University 4Space Bio-Laboratories Co., Ltd., Japan 5Natural Science Center for Basic Research and Development, Hiroshima University, Japan 6Department of Radiation Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Japan *Corresponding author: Louis Yuge, Division of Bio-Environmental Adaptation Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan, Tel: 81-82257-5425; Fax: 81-82-257-5344; E-mail: [email protected] Received January 04, 2017; Accepted January 30, 2017; Published January 31, 2017 Citation: Imura T, Tomiyasu M, Otsuru N, Nakagawa K, Otsuka T, et al. (2017) Hypoxic Preconditioning Increases the Neuroprotective Effects of Mesenchymal Stem Cells in a Rat Model of Spinal Cord Injury. J Stem Cell Res Ther 7: 375. doi: 10.4172/2157-7633.1000375 Copyright: © 2017 Imura T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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تاریخ انتشار 2017