Cytotherapeutics, Inc.

Brown University

Neurotech S.a.

Laura M Holland

Frank T Gentile

Edward J Doherty

Joseph P Hammang

Patrick Aebischer

Molly S Shoichet

Shelley R Winn

Brian M Cain

Malcolm Schinstine

Patrick A Tresco

David H Rein

Tyrone F Hazlett

Thomas Flanagan

Keith E Dionne

Michael J Lysaght

Seth A Rudnick

A method for determining the viral retentivity of an external jacket of an implantable permselective macrocapsule. Viral retentivity describes the ability of an external jacket to retard the transport of virus particles across the jacket.

Microporous macrocapsules

This invention relates to methods and compositions of controlling cell distribution within a 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 BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.

Methods and compositions of growth control for cells encapsulated within

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. The bioartificial organ typically has a semipermeable membrane encapsulating a cell-containing core, and is preferably immunoisolatory. Cells can be grown on microcarriers and then loaded into the bioartificial organ. The microcarriers may be coated with an extracellular matrix component such as collagen to cause decreased cell proliferation or increased cell differentiation. Microcarriers containing cells can be suspended in a proliferation inhibiting hydrogel matrix prior to encapsulation.

Control of cell growth in a bioartificial organ with extracellular

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.

Controlling proliferation of cells before and after encapsulation in a

Methods and compositions are provided for controlling cell distribution within a 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. In a preferred treatment, cells are exposed to and then removed from exposure to a proliferation-stimulating and differentiation inhibiting compound prior to encapsulation of the cells in a semipermeable biocompatible jacket to form a bioartificial organ. Upon in vivo implantation of the bioartificial organ in a host, cellular proliferation is inhibited and cellular differentiation is promoted.

Method for controlling proliferation and differentiation of cells

This invention relates to methods and compositions of controlling cell distribution within a 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 BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination. A particular embodiment is directed to derivatizing or adsorbing polyethylene oxide-poly(dimethylsiloxane) copolymer (PEO-PDMS) onto a surface within the bioartificial organ to inhibit cellular attachment.

Method for controlling the distribution of cells within a bioartificial

This invention provides methods for implanting encapsulated cells in a host comprising exposing cells to restrictive conditions for a sufficient period of time to establish a desired cell property in response to the restrictive conditions and implanting the encapsulated cells in a host, the cell property being substantially maintained following implantation. Also provided are cells produced by exposure to restrictive conditions.

Growing community of inventors

Horsham, PA, United States of America

Laura M Holland