Method to reproduce circadian rhythms on a microfluidic chip
AssigneeYissum Research Development Company of the Hebrew University of Jerusalem
InventorYaakov Nahmias
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Abstract
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.
Claims23
An in-vitro method of sustaining a synchronized circadian rhythm in mammalian cells a in cell culture, the method comprising:
- exposing the mammalian cells to a continuous flow of medium with a constant total volumetric flow rate in which at least two hormones are present in an oscillating manner with a periodicity of 24±4 hours,
- wherein a first hormone and a second hormone of said at least two hormones are distinct,
- wherein said exposing comprises flowing over said mammalian cells in culture a first medium comprising said first hormone, a second medium comprising said second hormone, a third medium devoid of said first hormone and said second hormone or a combination of said media and wherein changing concentrations of said at least two hormones are exposed to said mammalian cells by varying a volumetric flow rate of each of said media while keeping a constant total volumetric flow rate over the cells,
- wherein an interval between a maximum concentration of said first hormone exposed to said mammalian cells and a maximum concentration of said second hormone exposed to said mammalian cells is at least 2 hours,
- and wherein said first hormone is selected from the group consisting of:
- cortisol, testosterone, adiponectin, insulin, thyroxine (T4), and fibroblast growth factor 21 (FGF21), and said second hormone is selected from the group consisting of:
- melatonin, growth hormone, Triiodothyronine (T3), ghrelin, prolactin, TSH, vasopressin, and leptin,
- thereby sustaining a synchronized circadian rhythm in mammalian cells in a cell culture.
Dependencies are inferred from the claim text.