Mucosal cell composites and methods
AssigneeThe Regents of the University of Michigan
InventorsStephen E. Feinberg, Cynthia L. Marcelo, Blake J. Roessler
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Abstract
The present invention discloses a composite made of a layer of epithelial cells cultured together with a dermal matrix in a culture medium, which is free of BPE. The dermal matrix is a substantially non-immunogenic human dermis. Also disclosed is an enhanced composite where a biological agent has been introduced into the epithelial cells. The invention also comprises methods of making and implanting both the composite and the enhanced composite in an animal. A method of treating disease or injury through the use of the disclosed composites is also part of the present invention.
Claims48
A mucosal membrane equivalent comprising:
- an epithelial layer including epithelial cells;
- and
- a dermal matrix layer,
- wherein the epithelial layer and the dermal matrix layer form a composite and are substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract and wherein the epithelial cells are transduced or transfected to deliver a biological agent.
A method of making a mucosal membrane equivalent comprising:
- culturing epithelial cells with a dermal matrix to form a unitary construct, wherein the culturing step includes culturing the epithelial cells and dermal matrix in a defined culture medium that is substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract.
A method of making a mucosal membrane equivalent comprising:
- culturing epithelial cells with a dermal matrix in a defined culture medium that is substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract to form a unitary construct, wherein the culturing step includes culturing the epithelial cells and dermal matrix construct in a submerged state and culturing the epithelial cells and dermal matrix at an air/liquid interface after culturing in the submerged state.
A method of making a mucosal membrane equivalent comprising:
- culturing epithelial cells with a dermal matrix in a defined culture medium that is substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract to form a unitary construct, wherein the culturing step includes seeding keratinocytes onto the dermal matrix and wherein the keratinocytes are conjunctival mucosal cells.
A method of making a mucosal membrane equivalent comprising:
- culturing epithelial cells with a dermal matrix to form a unitary construct, wherein the culturing step includes:
- presoaking the dermal matrix in a defined culture medium;
- seeding keratinocytes onto the dermal matrix to form a unitary construct;
- culturing the unitary construct in a submerged state in a defined culture medium that is substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract;
- and
- culturing the unitary construct at an air/liquid interface.
A method of making a mucosal membrane equivalent comprising:
- culturing epithelial cells with a dermal matrix in a defined culture medium that is substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract to form a composite, wherein the culturing step includes transducing or transfecting the epithelial cells to deliver a biological agent.
A method of using a mucosal membrane equivalent comprising:
- implanting a composite into a mammal, wherein the composite is comprised of an epithelial layer including epithelial cells and a dermal matrix layer that are substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract and wherein the epithelial cells are transduced or transfected to deliver a biological agent to the mammal.
A method of treating a mammal for disease or injury comprising:
- implanting, at a disease or injury site, a composite into a mammal, wherein the composite is comprised of an epithelial layer including epithelial cells and a dermal matrix layer that are substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract and wherein the epithelial cells are transduced or transfected to deliver a biological agent to the mammal.
A method of treating a mammal for disease or injury comprising:
- implanting, at a disease or injury site, a composite into a mammal, wherein the composite is comprised of an epithelial layer including epithelial cells and a dermal matrix layer that are substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract and wherein the epithelial cells are transduced or transfected to deliver a nucleic acid to the mammal.
A mucosal membrane equivalent comprising:
- an epithelial layer including epithelial cells;
- and
- a dermal matrix layer,
- wherein the epithelial layer and the dermal matrix layer form a composite and
- wherein the composite is substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract.
A method of making a mucosal membrane equivalent comprising:
- culturing epithelial cells with a dermal matrix in a defined culture medium that is substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract to form a composite.
A method of using a mucosal membrane equivalent comprising:
- implanting a composite into a mammal, wherein the composite is comprised of an epithelial layer including epithelial cells and a dermal matrix layer that are substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract.
A method of making a mucosal membrane equivalent comprising:
- culturing epithelial cells with a dermal matrix to form a composite, wherein the culturing step includes:
- presoaking the dermal matrix in a defined culture medium;
- seeding keratinocytes onto the dermal matrix to form a composite;
- culturing the composite in a submerged state in a defined culture medium that is substantially free of serum, transformed irradiated feeder cells, and bovine pituitary extract;
- and
- culturing the composite at an air/liquid interface.
Dependencies are inferred from the claim text.