Development of a kinetic model expressing anomalous phenomena in human induced pluripotent stem cell culture

Abstract

During culture with feeder cells, deviation from the undifferentiated state of human induced pluripotent stem cells (hiPSCs) occurs at a very low frequency. Anomalous cell migration in central and peripheral regions of hiPSC colonies has been suggested to be the trigger for this phenomenon. To confirm this hypothesis, sequential cell migration prior to deviation must be demonstrated. This has been difficult using invitro methods. We therefore developed a kinetic model with a proposed definition of anomalous cell migration as continuous relatively fast or slow cell migration. The developed model was validated via in silico reproduction of deviation phenomenon observed invitro, such as the positions of deviated cells in a colony and the frequency of deviation in culture. This model suggests that anomalous cell migration-driven hiPSC deviation can be explained by two factors: a mechanical stimulus, represented by cell migration, and duration of the mechanical stimulus. The factor "duration of mechanical stimulus" sets our model apart from others, and helps to realize the ultra-rare trigger (approximately 10-5) of deviation from the undifferentiated state in hiPSC culture.