for a cytotoxic effect (Bordessa et al., 2014). From the highest concentration without a clear cytotoxic effect and its Cmax in vivo, a safety margin (SM) was calculated for each TC. An SM < 10 was set as identification of a DILI risk (Mueller et al., 2015). In to calculate hepatocyte- only responses for ATP in micropatterned co-cultures (HepatoPac), cellular ATP levels were also determined in stromal-only cultures (i.e. murine 3T3 fibroblasts). ATP signals in stromal-only control cultures were subtracted from those of HepatoPacTM co-cultures to obtain hepatocyte-specific effects. Results and Discussion Viability profiles in Suspended Pooled Human Hepatocytes Figure 1 shows the viability profiles obtained with the pool of cryopreserved human hepatocytes (P0203T n = 13 donors) exposed for 2 hours to the 16 TCs compared to the mean viability profiles obtained with plated cryopreserved human hepatocyte preparations in 2D-sw monoculture (n = 3 - 5 donors) exposed for 24 hours.
for a cytotoxic effect (Bordessa et al., 2014). From the highest concentration without a clear cytotoxic effect and its Cmax in vivo, a safety margin (SM) was calculated for each TC. An SM < 10 was set as identification of a DILI risk (Mueller et al., 2015). In to calculate hepatocyte- only responses for ATP in micropatterned co-cultures (HepatoPac), cellular ATP levels were also determined in stromal-only cultures (i.e. murine 3T3 fibroblasts). ATP signals in stromal-only control cultures were subtracted from those of HepatoPacTM co-cultures to obtain hepatocyte-specific effects. Results and Discussion Viability profiles in Suspended Pooled Human Hepatocytes Figure 1 shows the viability profiles obtained with the pool of cryopreserved human hepatocytes (P0203T n = 13 donors) exposed for 2 hours to the 16 TCs compared to the mean viability profiles obtained with plated cryopreserved human hepatocyte preparations in 2D-sw monoculture (n = 3 - 5 donors) exposed for 24 hours.
Revised%20-%20cytotoxicity%20evaluation.docx