Provided are in-vitro methods and devices for sustaining a synchronized circadian rhythm in cells of a cell culture by exposing the cells to a continuous flow of medium and to at least two stimuli provided in an oscillating manner with a periodicity of 24±4 hours, wherein a first stimulus and a second stimulus of said at least two stimuli are distinct, wherein said first stimulus is provided in a first time period and reaches a first peak in a first peak time period, and wherein a second stimulus is provided in a second time period and reaches a second peak in a second peak time period, and wherein an interval between end of time period of said first peak and beginning of said time period of said second peak is at least about 2 hours.