title: Differential Effects of Isoxazole-9 on Neural Stem/Progenitor Cells, Oligodendrocyte Precursor Cells, and Endothelial Progenitor Cells.
abstract: Adult mammalian brain can be plastic after injury and disease. Therefore, boosting endogenous repair mechanisms would be a useful therapeutic approach for neurological disorders. Isoxazole-9 (Isx-9) has been reported to enhance neurogenesis from neural stem/progenitor cells (NSPCs). However, the effects of Isx-9 on other types of progenitor/precursor cells remain mostly unknown. In this study, we investigated the effects of Isx-9 on the three major populations of progenitor/precursor cells in brain: NSPCs, oligodendrocyte precursor cells (OPCs), and endothelial progenitor cells (EPCs). Cultured primary NSPCs, OPCs, or EPCs were treated with various concentrations of Isx-9 (6.25, 12.5, 25, 50 μM), and their cell numbers were counted in a blinded manner. Isx-9 slightly increased the number of NSPCs and effectively induced neuronal differentiation of NSPCs. However, Isx-9 significantly decreased OPC number in a concentration-dependent manner, suggesting cytotoxicity. Isx-9 did not affect EPC cell number. But in a matrigel assay of angiogenesis, Isx-9 significantly inhibited tube formation in outgrowth endothelial cells derived from EPCs. This potential anti-tube-formation effect of Isx-9 was confirmed in a brain endothelial cell line. Taken together, our data suggest that mechanisms and targets for promoting stem/progenitor cells in the central nervous system may significantly differ between cell types.
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America; Department of Neurology, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Koh
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Liang
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America; Department of Developmental Neuroscience, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Takakuni
authors.initials: T
authors.lastname: Maki
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Shindo
authors.affiliation: Department of Developmental Neuroscience, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Osumi
authors.affiliation: Regenerative Medicine Discovery Performance Unit, GlaxoSmithKline, Cambridge, Massachusetts, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Regenerative Medicine Discovery Performance Unit, GlaxoSmithKline, Cambridge, Massachusetts, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Lin
authors.affiliation: Regenerative Medicine Discovery Performance Unit, GlaxoSmithKline, Cambridge, Massachusetts, United States of America.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Holder
authors.affiliation: Regenerative Medicine Discovery Performance Unit, GlaxoSmithKline, Cambridge, Massachusetts, United States of America.
authors.forename: Tsu Tshen
authors.initials: TT
authors.lastname: Chuang
authors.affiliation: Regenerative Medicine Discovery Performance Unit, GlaxoSmithKline, Cambridge, Massachusetts, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: McNeish
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Ken
authors.initials: K
authors.lastname: Arai
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
mesh_terms: D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D051381:Rats
chemical_list: D015415:Biomarkers; D007555:Isoxazoles