A novel cell transplantation protocol and its application to an ALS mouse model |
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Authors: | Morita Eri Watanabe Yasuhiro Ishimoto Miho Nakano Toshiya Kitayama Michio Yasui Kenichi Fukada Yasuyo Doi Koji Karunaratne Asanka Murrell Wayne G Sutharsan Ratneswary Mackay-Sim Alan Hata Yoshio Nakashima Kenji |
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Institution: | aDepartment of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1 Nishico-cho, Yonago 683-8504, Japan;bDivision of Neurobiology, School of Life Science, Tottori University Graduate School of Medical Science, Yonago 683-8504, Japan;cNational Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland 4111, Australia;dDepartment of Integrative Bioscience, Tottori University Graduate School of Medical Science, Yonago 683-8504, Japan |
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Abstract: | Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease, which selectively affects motor neurons throughout the central nervous system. The extensive distribution of motor neurons is an obstacle to applying cell transplantation therapy for the treatment of ALS. To overcome this problem, we developed a cell transplantation method via the fourth cerebral ventricle in mice. We used mouse olfactory ensheathing cells (OECs) and rat mesenchymal stem cells (MSCs) as donor cells. OECs are reported to promote regeneration and remyelination in the spinal cord, while MSCs have a capability to differentiate into several types of specific cells including neural cells. Furthermore both types of cells can be relatively easily obtained by biopsy in human. Initially, we confirmed the safety of the operative procedure and broad distribution of grafted cells in the spinal cord using wild-type mice. After transplantation, OECs distributed widely and survived as long as 100 days after transplantation, with a time-dependent depletion of cell number. In ALS model mice, OEC transplantation revealed no adverse effects but no significant differences in clinical evaluation were found between OEC-treated and non-transplanted animals. After MSC transplantation into the ALS model mice, females, but not males, showed a statistically longer disease duration than the non-transplanted controls. We conclude that intrathecal transplantation could be a promising way to deliver donor cells to the central nervous system. Further experiments to elucidate relevant conditions for optimal outcomes are required. |
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Keywords: | Amyotrophic lateral sclerosis Transplantation Intrathecal Olfactory ensheathing cell Mesenchymal stem cell |
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