A novel cell transplantation protocol and its application to an ALS mouse model

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Title A novel cell transplantation protocol and its application to an ALS mouse model
Author Morita, Eri; Watanabe, Yauhiro; Ishimoto, Miho; Nakano, Toshiya; Kitayama, Michio; Yasui, Kenichi; Fukada, Yasuyo; Doi, Koji; Karunaratne, Asanka Manjula; Murrell, Wayne George; Sutharsan, Ratneswary; Mackay-Sim, Alan; Hata, Yoshio; Nakashima, Kenji
Journal Name Experimental Neurology
Editor S Gilman (Editor-in-Chief)
Year Published 2008
Place of publication United States
Publisher Academic Press / Elsevier
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 ansplantation 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.
Peer Reviewed Yes
Published Yes
Publisher URI http://www.sciencedirect.com/science/journal/00144886
Alternative URI http://dx.doi.org/10.1016/j.expneurol.2008.07.011
Volume 213
Issue Number 2
Page from 431
Page to 438
ISSN 0014-4886
Date Accessioned 2009-02-05
Language en_AU
Research Centre Eskitis Institute for Drug Discovery
Faculty Faculty of Science, Environment, Engineering and Technology
Subject PRE2009-Neurology and Neuromuscular Diseases; PRE2009-Sensory Systems
URI http://hdl.handle.net/10072/22515
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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