고성호
2017-05-23T04:56:54Z
2017-05-23T04:56:54Z
2015-09
PLOS ONE, v. 10, NO 9, Page. 1-16
1932-6203
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138724
http://hdl.handle.net/20.500.11754/27407
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 mu M), 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.
Work was supported in part by grants from the National Institutes of Health (P01-NS55104), the Uehara Memorial Foundation, and the Glaxo-Smith-Kline-Harvard-Stem-Cell-Institute consortium. Salaries for authors with primary appointments with Glaxo-Smith-Kline (JZ, HL, JCH, TTC, and JDM) were paid by Glaxo-Smith-Kline. JZ, HL, JCH, TTC, and JDM participated in study design and data analysis.
en
PUBLIC LIBRARY SCIENCE
STROKE RECOVERY
SMALL-MOLECULE
STEM-CELLS
BRAIN
ANGIOGENESIS
NEUROGENESIS
PROLIFERATION
TRANSLATION
THERAPY
FATE
Differential Effects of Isoxazole-9 on Neural Stem/Progenitor Cells, Oligodendrocyte Precursor Cells, and Endothelial Progenitor Cells
Article
9
10
10.1371/journal.pone.0138724
1-16
PLOS ONE
Koh, Seong-Ho
Liang, Anna C.
Takahashi, Yoko
Maki, Takakuni
Shindo, Akihiro
Osumi, Noriko
Zhao, Jing
Lin, Hong
Holder, Julie C.
Chuang, Tsu Tshen
2015008685
S
COLLEGE OF MEDICINE[S]
DEPARTMENT OF MEDICINE
ksh213