Differential effects of isoxazole-9 on neural stem/progenitor cells, oligodendrocyte precursor cells, and endothelial progenitor cells

Seong Ho Koh, Anna C. Liang, Yoko Takahashi, Takakuni Maki, Akihiro Shindo, Noriko Osumi, Jing Zhao, Hong Lin, Julie C. Holder, Tsu Tshen Chuang, John D. McNeish, Ken Arai, Eng H. Lo

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Article numbere0138724
JournalPloS one
Volume10
Issue number9
DOIs
Publication statusPublished - 2015 Sep 25

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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