Back to results
US 9,500,642 B2Granted
In vitro model for pathological or physiologic conditions
AssigneeHemoShear, LLC
InventorsBrett R. Blackman, Brian R. Wamhoff, Ajit Dash, Michael B. Simmers, Ryan E. Feaver
Life of this patent
Estimating the term…
Abstract
The present invention generally relates to in vitro methods for mimicking in vivo pathological or physiologic conditions. The methods comprise applying shear forces to a cell type or cell type plated on a surface within a cell culture container. Methods for testing drugs or compounds in such systems are also described.
Claims61
A method of mimicking a physiologic condition of the liver in vitro, the method comprising:
- a) adding a culture medium and at least one factor to a cell culture container;
- b) plating at least one hepatic cell type on at least one surface within the cell culture container;
- and
- c) applying a shear force upon the at least one plated hepatic cell type, the shear force resulting from flow of the culture medium induced by a flow device, the flow mimicking flow to which the at least one hepatic cell type is exposed in vivo in the physiologic condition, wherein the factor is exogenously added to the cell culture container to provide a concentration that is:
- (i) within the in vivo concentration range of the factor observed in the physiologic condition;
- (ii) within the concentration range of the factor that would result in vivo from administration of a drug or a compound;
- or
- (iii) capable of maintaining the mimicked physiologic condition in vitro for a period of time under the shear force, the same concentration of factor being incapable of maintaining the mimicked physiologic condition in vitro for the period of time in the absence of the shear force;
- and wherein the at least one plated hepatic cell type comprises hepatocytes and wherein a measurement of responsiveness to glucagon, insulin, or a substrate for glucose synthesis in the hepatocytes confirms mimicking of the physiologic condition.
6 more elements
A method of mimicking a pathological or physiologic condition in vitro, the method comprising:
- a) adding a culture medium and serum from a subject comprising at least one factor to a cell culture container;
- b) plating at least one cell type on at least one surface within the cell culture container;
- and
- c) applying a shear force upon the at least one plated cell type, the shear force resulting from flow of the culture medium induced by a flow device, the flow mimicking flow to which the at least one cell type is exposed in vivo in the pathological or physiologic condition, wherein,
- for mimicking the pathological condition, the factor is exogenously added to the cell culture container to provide a concentration that is either:
- (i) within the in vivo concentration range of the factor observed in the pathological condition;
- or
- (ii) within the concentration range of the factor that would result in vivo from administration of a drug or a compound;
- or
- for mimicking the physiologic condition, the factor is exogenously added to the cell culture container to provide a concentration that is
- within the concentration range of the factor that would result in vivo from administration of a drug or a compound.
8 more elements
A method of mimicking a pathological or physiologic condition in vitro, the method comprising:
- a) adding a culture medium and at least one factor to a cell culture container;
- b) plating at least one cell type on at least one surface within the cell culture container, wherein the at least one cell type comprises primary cells, the primary cells comprising inducible pluripotent stem cell (iPSC)-derived cells from a subject having a pathological condition;
- and
- c) applying a shear force upon the at least one plated cell type, the shear force resulting from flow of the culture medium induced by a flow device, the flow mimicking flow to which the at least one cell type is exposed in vivo in the pathological or physiologic condition, wherein,
- for mimicking the pathological condition, the factor is exogenously added to the cell culture container to provide a concentration that is either:
- (i) within the in vivo concentration range of the factor observed in the pathological condition;
- or
- (ii) within the concentration range of the factor that would result in vivo from administration of a drug or a compound;
- or
- for mimicking the physiologic condition, the factor is exogenously added to the cell culture container to provide a concentration that is either:
- (i) within the in vivo concentration range of the factor observed in the physiologic condition;
- or
- (ii) within the concentration range of the factor that would result in vivo from administration of a drug or a compound.
10 more elements
Dependencies are inferred from the claim text.