title: A novel cell transplantation protocol and its application to an ALS mouse model.
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.
authors.affiliation: Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Morita
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Miho
authors.initials: M
authors.lastname: Ishimoto
authors.forename: Toshiya
authors.initials: T
authors.lastname: Nakano
authors.forename: Michio
authors.initials: M
authors.lastname: Kitayama
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yasui
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Fukada
authors.forename: Koji
authors.initials: K
authors.lastname: Doi
authors.forename: Asanka
authors.initials: A
authors.lastname: Karunaratne
authors.forename: Wayne G
authors.initials: WG
authors.lastname: Murrell
authors.forename: Ratneswary
authors.initials: R
authors.lastname: Sutharsan
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay-Sim
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hata
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakashima
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology / Q000601:surgery*; D000818:Animals; D017690:Cell Transplantation / Q000379:methods / Q000639:trends; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009831:Olfactory Mucosa / Q000166:cytology / Q000637:transplantation; D051381:Rats