Advance Access publication February 21, 2011 Assessment of Chemical-Induced Impairment of Human Neurite Outgrowth by Multiparametric Live Cell Imaging in High-Density Cultures

Chemicals that specifically alter human neurite outgrowth pose a hazard for the development of the nervous system. The identification of such compounds remains a major challenge, especially in a human test system. To address this issue, we developed an imaging-based procedure in LUHMES human neuronal precursor cells to quantify neurite growth of unfixed cultures. Live imaging allowed the simultaneous evaluation of cell viability and neurite outgrowth within one culture dish. The procedure was used to test the hypothesis that inhibitors of specific pathways can impair neurite outgrowth without affecting cell viability. Although the cells were grown at high density to allow extensive networking, overall neurite growth in this complex culture was quantified with a signal-to-noise ratio of> 50. Compounds such as U0126 slowed the extension of neuronal processes at concentrations> 4 times lower than those causing cel