Propofol is an intravenous anesthetic that has been widely used in the clinical setting. Besides its anesthetic effects, propofol has been reported to influence the regulation of autonomic system. Controversies exist with regards to whether propofol exposure is safe for pregnant women and young children. The recent emergence of human induced pluripotent stem cells (hiPSCs) has provided a promising and theoretically inexhaustible source of neural progenitor cells (NPCs) for drug testing, which could be extended to in vitro experiments for anesthetics such as propofol. NPCs derived from three hiPSC lines, NES-GFP (a NESTIN-GFP reporter), USCK7 (iPSCs derived from urine derived cells), and ND2-0 (NIH), were treated with propofol at different concentrations (20, 50, 100 and 300 μM) for 6 h or 24 h. Early and late cell injury, cell proliferation and apoptosis were evaluated. Comparison of genome-wide gene expression profiles was performed for propofol-treated and untreated control iPSC-NPCs. Propofol treatment of NPCs for 6 h at the clinically relevant concentration (20 or 50 μM) did not affect cell viability, apoptosis, or proliferation, while propofol at higher concentration (100 or 300 μM) decreased NPC viability and induced apoptosis. Prolonged treatment of propofol for 24 h significantly decreased cell viability. In addition, 20 μM propofol treatment for 6 h did not alter global gene expression. Higher concentration of propofol exerted potential cytotoxicity via multiple cellular mechanisms. In summary, propofol treatment at commonly practiced clinical doses for 6 h did not have adverse effects on hiPSC-derived NPCs. In contrast, longer exposure and/or higher concentration of propofol treatment could decrease NPC viability and induce apoptosis.

TRIB3, CEBPB, DDIT3, ATF4, CEBPB, TRIB3, HSPA5