P3‐136: A Genetically Immortalized Human Stem Cell Line: A Promising New Tool for Alzheimer’s Disease Therapy

Background:Amyloid-b peptide and hyperphosphorylated tau are the main pathological hallmarks of Alzheimer’s disease (AD) (Reitz et al., 2014). Given the recent failure of several large-scale clinical trials and the lack of disease-modifying pharmacological treatments, there is an urgent need to develop alternative therapies. CTX0E03 is a clinical-grade human neural stem cell line which has recently passed phase I trials in people with stroke (Hick et al., 2013). However, this line has not been investigated in other neurodegenerative disorders. Methods: CTX0E03 cells were seeded into laminin-precoated 96-well plates at cell density 5x10 cells/ml. Cells were treated with amyloid peptides (Ab1-40 and Ab1-42) at concentrations of 0.5, 1, 5, 10, and 15 mM and okadaic acid (OA) at 0.5, 1, 5, 10, and 15 nM. Vehicle control cultures were treated with 0.1% DMSO or PBS (control for OA and Ab respectively). After 24 h incubation, the cells were examined for cell viability using PrestoBlue reagent and lactate dehydrogenase-cytotoxicity assay. Results: Cell viability assays showed a concentration dependence of this cell line to the toxic effects of Ab1-42, but not Ab1-40, and OA. Notably, CTX0E03 cell line displayed toxicity at concentrations significantly higher than both rat neural stem cells and those previously reported for primary cultures. Conclusions:Our study indicates the ability of clinical grade CTX0E03 stem cell line to resist the inhospitable milieu associated with AD. Thus, CTX0E03 stem cells provide a potential candidate for cell therapy in AD patients.