Comment on "Drug screening for ALS using patient-specific induced pluripotent stem cells"

Abstract

Egawa et al. recently showed the value of patient-specific induced pluripotent stem cells (iPSCs) for modeling amyotrophic lateral sclerosis in vitro. Their study and our work highlight the need for complementary assays to detect small, but potentially important, phenotypic differences between control iPSC lines and those carrying disease mutations.

Fig. 1. Survival of ALS mutant versus control iPSC-derived motor neurons

(A) Comparison of cell death in motor neuronal cultures derived from two clones of mutant M337V TDP-43 iPSCs from one ALS patient (M337V-1 and M337V-2) and two control iPSC lines (from two different individuals; Control-1 and Control-2) under basal conditions using an LDH release assay (2). LDH release into the culture medium was normalized to total LDH after cell lysis for each well to determine percent cytotoxicity. Values are mean ± SEM. Data were analyzed by one-way ANOVA. There were no significant differences between the mean survival for motor neurons derived from mutant M337V TDP-43 iPSCs versus control iPSCs (n=4). (B) Cell survival of two independent control iPSC-derived motor neuronal cultures transfected with a HB9::GFP reporter construct. Cell survival was measured by counting the number of GFP-positive neurons over the course of nine days (2). The cell count on day 1 for each experiment was set to 100% and each time point after that was expressed as a percent of the value at day 1. Values are mean ± SEM, n=4. There were no significant differences in mean survival between day 1 and day 9.