title: Allogeneic bone marrow stromal cells promote glial-axonal remodeling without immunologic sensitization after stroke in rats.
abstract: We evaluated the effects of allogeneic bone marrow stromal cell treatment of stroke on functional outcome, glial-axonal architecture, and immune reaction. Female Wistar rats were subjected to 2 h of middle cerebral artery occlusion. Rats were injected intravenously with PBS, male allogeneic ACI--or syngeneic Wistar--bone marrow stromal cells at 24 h after ischemia and sacrificed at 28 days. Significant functional recovery was found in both cell-treated groups compared to stroke rats that did not receive BMSCs, but no difference was detected between allogeneic and syngeneic cell-treated rats. No evidence of T cell priming or humoral antibody production to marrow stromal cells was found in recipient rats after treatment with allogeneic cells. Similar numbers of Y-chromosome+ cells were detected in the female rat brains in both groups. Significantly increased thickness of individual axons and myelin, and areas of the corpus callosum and the numbers of white matter bundles in the striatum were detected in the ischemic boundary zone of cell-treated rats compared to stroked rats. The areas of the contralateral corpus callosum significantly increased after cell treatment compared to normal rats. Processes of astrocytes remodeled from hypertrophic star-like to tadpole-like shape and oriented parallel to the ischemic regions after cell treatment. Axonal projections emanating from individual parenchymal neurons exhibited an overall orientation parallel to elongated radial processes of reactive astrocytes of the cell-treated rats. Allogeneic and syngeneic bone marrow stromal cell treatment after stroke in rats improved neurological recovery and enhanced reactive oligodendrocyte and astrocyte related axonal remodeling with no indication of immunologic sensitization in adult rat brain.
authors.affiliation: Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Kevin
authors.initials: K
authors.lastname: McIntosh
authors.forename: Jieli
authors.initials: J
authors.lastname: Chen
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.forename: Jade
authors.initials: J
authors.lastname: Borneman
authors.forename: Kim
authors.initials: K
authors.lastname: Raginski
authors.forename: James
authors.initials: J
authors.lastname: Mitchell
authors.forename: Lihong
authors.initials: L
authors.lastname: Shen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Dunyue
authors.initials: D
authors.lastname: Lu
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D001522:Behavior, Animal; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007111:Immunity, Cellular / Q000502:physiology; D017403:In Situ Hybridization / Q000379:methods; D008214:Lymphocytes / Q000502:physiology / Q000528:radiation effects; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009186:Myelin Sheath / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology; D009460:Neurologic Examination / Q000379:methods; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology; D020521:Stroke / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D017154:Stromal Cells / Q000502:physiology*; D013997:Time Factors; D014184:Transplantation, Homologous / Q000379:methods; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism; D014998:Y Chromosome / Q000235:genetics / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D001973:Bromodeoxyuridine