Use of steady-state oxygen gradients to modulate animal cell functions
First Claim
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1. A method comprising:
- controlling an oxygen gradient across a population of cells in one or more bioreactors to modify a tissue morphology, function, and/or gene expression.
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Abstract
The disclosure provides a bioreactor that allows steady-state oxygen gradients to be imposed upon in vitro culture systems. The bioreactor system of the disclosure has been applied to liver zonation and have shown that physiological oxygen gradients contribute to heterogeneity of tissue cultures in vitro.
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Citations
71 Claims
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1. A method comprising:
controlling an oxygen gradient across a population of cells in one or more bioreactors to modify a tissue morphology, function, and/or gene expression. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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21. A bioreactor comprising:
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at least one housing having an inlet port and an outlet port;
at least one substrate disposed in the at least one housing;
at least one tissue binding surface on each of the at least one substrate, the housing and tissue binding surface defining a flow space along the tissue binding surface;
a pump in fluid communication with the inlet port and the outlet port of the housing;
a gas exchange device disposed between the pump and the inlet port;
a fluid reservoir in fluid communication with the pump; and
a gas sensor disposed between the outlet port and the fluid reservoir, wherein the pump, the gas exchange device, the flow space, the gas sensor and the fluid reservoir are in fluid communication, such that a fluid is pumped from the fluid reservoir through (i) the gas exchanger, (ii) the flow space, (iii) the gas sensor and returned to the fluid reservoir using the pump and wherein the gas concentration is modulated by the gas exchange device and sensed by the gas sensor. - View Dependent Claims (22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41)
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42. A method of producing a tissue, comprising:
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seeding a population of cells on a substrate in a bioreactor system;
controlling an oxygen gradient across the population of cells in one or more bioreactors;
culturing the cells under conditions and for a sufficient period of time to generate a tissue. - View Dependent Claims (43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71)
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Specification