Controlling proliferation of cells before and after encapsulation in a bioartificial organ by gene transformation
First Claim
1. A method for controlling distribution of cells within an implantable bioartificial organ comprising the steps of:
- (a) transforming the cells with a proliferation-promoting gene operatively linked to a regulatable promoter wherein the regulatable promoter is activated in vitro to achieve expression of the proliferation-promoting gene, resulting in proliferation of the transformed cells in vitro; and
(b) inserting the cells from (a) in a bioartificial organ and inactivating the regulatable promoter either before or after inserting the cells in the bioartificial organ such that expression of the proliferation-promoting gene is inhibited to reduce or stop proliferation of the cells in the bioartificial organ in vivo in a host.
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Accused Products
Abstract
Methods and compositions are provided for controlling cell distribution within an implantable bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the bioartificial organ with extracellular matrix molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination. Cells can be transformed with a proliferation-promoting gene such as the oncogene, SV40, linked to a regulatable promoter such as the Mx1 promoter, the promotor is activated in vitro to express the gene to result in cell proliferation, and the promotor is inactivated before or after insertion of the cells in the bioartificial organ to inhibit expression of the gene to reduce or stop cell proliferation in vivo. The promoter can be reactivated in vivo to again express the gene to result in further cell proliferation. The gene may be a proliferation-suppressing gene such as p53 gene or RB gene, or a differentiation-inducing gene such as high mobility group chromosomal protein 14. Inhibiting gene expression in vitro causes cell proliferation, and inducing gene expression reduces or stops cell proliferation in vivo.
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Citations
10 Claims
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1. A method for controlling distribution of cells within an implantable bioartificial organ comprising the steps of:
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(a) transforming the cells with a proliferation-promoting gene operatively linked to a regulatable promoter wherein the regulatable promoter is activated in vitro to achieve expression of the proliferation-promoting gene, resulting in proliferation of the transformed cells in vitro; and (b) inserting the cells from (a) in a bioartificial organ and inactivating the regulatable promoter either before or after inserting the cells in the bioartificial organ such that expression of the proliferation-promoting gene is inhibited to reduce or stop proliferation of the cells in the bioartificial organ in vivo in a host. - View Dependent Claims (2, 3, 4, 5, 6)
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7. A method for controlling distribution of cells within an implantable bioartificial organ comprising the steps of:
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(a) transforming the cells with a proliferation-suppressing gene operatively linked to a regulatable promoter wherein the regulatable promoter is inactivated in vitro to inhibit expression of the proliferation-suppressing gene, resulting in proliferation of the transformed cells in vitro; and (b) inserting the cells from (a) in a bioartificial organ and activating the regulatable promoter either before or after inserting the cells in the bioartificial organ such that expression of the proliferation-suppressing gene occurs to reduce or stop proliferation of the cells in the bioartificial organ in vivo in a host. - View Dependent Claims (8)
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9. A method for controlling distribution of cells within an implantable bioartificial organ comprising the steps of:
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(a) transforming the cells with a differentiation-inducing gene operatively linked to a regulatable promoter wherein the regulatable promoter is inactivated in vitro to inhibit expression of the differentiation-inducing gene, resulting in proliferation of the transformed cells invtro; and (b) inserting the cells from (a) in a bioartificial organ and activating the regulatable promoter either before or after inserting the cells in the bioartificial organ such that expression of the differentiation-inducing gene occurs to reduce or stop proliferation of the cells in the bioartificial organ in vivo in a host. - View Dependent Claims (10)
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Specification