Abstract: The invention provides a method for determining the effect of a biological agent comprising contacting a cell culture with a biological agent. The cell culture of the invention contains a culture medium containing one or more preselected growth factors effective for inducing multipotent central nervous system (CNS) neural stem cell proliferation. The cell culture also contains, suspended in the culture medium, human multipotent CNS neural stem cells that are derived from primary CNS neural tissue that have a doubling rate faster than 30 days.

Abstract: A method for producing analgesia or for neuroprotection in a mammal comprising administering a therapeutically effective amount of a conantokin to the mammal.

Abstract: Isolation, characterization, proliferation, differentiation and transplantation of mammalian neural stem cells is disclosed.

Abstract: Methods and devices are provided for gene therapy using encapsulated packaging cell lines to deliver viral particles carrying at least one heterologous gene encoding at least one biologically active molecule.

Abstract: Isolation, characterization, proliferation, differentiation and transplantation of mammalian neural stem cells is disclosed.

Abstract: 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.

Abstract: This invention provides improved devices and methods for long-term, stable expression of a biologically active molecule using a biocompatible capsule containing genetically engineered cells for the effective delivery of biologically active molecules to effect or enhance a biological function within a mammalian host. The novel capsules of this invention are biocompatible and are easily retrievable. This invention specifically provides improved methods and compositions which utilize cells transfected with recombinant DNA molecules comprising DNA sequences coding for biologically active molecules operatively linked to promoters that are not subject to down regulation in vivo upon implantation into a mammalian host. Furthermore, the methods of this invention allow for the long-term, stable and efficacious delivery of biologically active molecules from living cells to specific sites within a given mammal.

Abstract: The present invention provides novel devices and methods for continuous, controlled delivery of a biologically active molecule to the eye, either intraocularly or periocularly, to treat ophthalmic disorders. A capsule is surgically placed in the desired location in the eye. The capsule includes cells which produce the biologically active molecule. The capsule also includes a surrounding biocompatible jacket through which the biologically active molecule may diffuse into the eye. This jacket may immunoisolate the encapsulated cells, protecting them from attack by the immune system of the patient.

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. The bioartificial organ typically has a semipermeable membrane encapsulating a cell-containing core, and is preferably immunoisolatory.

Abstract: This invention relates to implantation of encapsulated PC12 cells capable of slowing or preventing the degenerative processes of Parkinson's disease by releasing factors in addition to dopamine into individuals suffering from the disease. This restorative effect continues even after the encapsulated cells are removed from the patient's brain.

Abstract: 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.

Abstract: A method for producing analgesia or for neuroprotection in a mammal comprising administering a therapeutically effective amount of a conantokin to the mammal.

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.

Abstract: 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.

Abstract: A bioartificial organ for implanting to provide a therapeutic effect is prepared containing a core of living cells encapsulated in a foam-like membrane having three regions: a dense, fine-pored, permselective inner region, a middle region that lacks macrovoids and a fine-pored outer region. The membrane has a molecular weight cutoff that permits passage to nutrients to the cells but not passage of the cells. Preferably, the membrane is made of polyether sulfone, pores range in size between 0.02 .mu.m and 2.0 .mu.m and have polyhedrally symmetric boundaries and are arranged asymmetrically from one surface to the other. The membrane has an asymmetry factor AF relative to the maximum pore diameter of 0.01 to 2.0 and a ratio of the maximum mean free path length to the diameter of the largest pore of greater than 3. The membrane can be hydrophobic or hydrophilic. The bioartificial organ is formed by coextrusion or by stepwise assembly by forming the cell core and then applying the membrane.

Abstract: 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.

Abstract: A bioartificial three-dimensional hydrogel extracellular matrix derivatized with a cell adhesive peptide fragment is provided for use in tissue regeneration or replacement. The choice of adhesive peptide fragment depends on the desired target cell type. Cartilage or tendon can be regenerated by implanting a matrix containing adhesive peptide fragments that favor chondrocyte invasion. The matrix can be pre-seeded with cells, and tissue can be reconstituted in vitro and then implanted. A cell-seeded matrix can be encapsulated in a semi-permeable membrane to form a bioartificial organ. An agarose hydrogel matrix having an agarose concentration of 0.5-1.25% (w/v) and an average gel pore radius between 120 nm and 290 nm is preferred. The peptide fragment preferably contains the sequence, ArgGlyAsp or TyrIleGlySerArg or IleLysValAlaVal, and is covalently immobilized to the matrix.

Abstract: 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.

Abstract: A biocompatible capsule for containing cells for implantation is prepared containing an inner support that provides tensile strength to the capsule. The capsule may be a tubular semipermeable membrane such as a hollow fiber membrane having both ends sealed. A rod shaped inner support extends through the lumen and ends of the rod are attached to sealed ends of the fiber. Prior to sealing one fiber end, cells are introduced into the lumen. Cells within the capsule may be suspended in a liquid medium or immobilized in a hydrogel or extracellular matrix material, and biologically active molecules can be delivered from the capsule to surroundings or from the surroundings into the capsule. The inner support may have external features such as flutes or a roughened or irregularly-shaped surface, and may be coated with cell-adhesive substance or a cell-viability-enhancing substance.

Abstract: 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.