Differential Effects of Isoxazole-9 on Neural Stem/Progenitor Cells, Oligodendrocyte Precursor Cells, and Endothelial Progenitor Cells

• Published in: PloS one 2015-09, Vol.10 (9), p.e0138724-e0138724
• Main Authors: Koh, Seong-Ho, Liang, Anna C, Takahashi, Yoko, Maki, Takakuni, Shindo, Akihiro, Osumi, Noriko, Zhao, Jing, Lin, Hong, Holder, Julie C, Chuang, Tsu Tshen, McNeish, John D, Arai, Ken, Lo, Eng H
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Biomarkers; Brain; Brain research; Cell Differentiation - drug effects; Cell number; Cell Proliferation - drug effects; Cells (biology); Cells, Cultured; Central nervous system; Cytotoxicity; Departments; Endothelial cells; Endothelial Progenitor Cells - cytology; Endothelial Progenitor Cells - drug effects; Endothelial Progenitor Cells - metabolism; Experiments; Glial stem cells; Hospitals; Isoxazoles - pharmacology; Laboratory animals; Medical schools; Medicine; Mice; Neural stem cells; Neural Stem Cells - cytology; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; Neurogenesis; Neurological diseases; Neurology; Neurons - cytology; Neurons - metabolism; Neurosciences; Oligodendroglia - cytology; Oligodendroglia - metabolism; Plasticity; Precursors; Progenitor cells; Rats; Rodents; Stem cells; Stroke; Toxicity
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0138724

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.