Abstract: The present invention provides compositions and methods for prevention and prophylaxis of neurological diseases accompanied by neuronal death. The invention includes synthesis of 5-benzylamino salicylic acid (BAS) and its derivatives. BAS and its derivatives protect cortical neurons from toxic insults by N-methyl-D-aspartate, Zn2+, and reactive oxygen species. Thus, the present invention provides compositions and methods for treating stroke, traumatic brain and spinal cord injury, epilepsy, and neurodegenerative diseases that are accompanied by severe neuronal loss via excitotoxicity, Zn2+ neurotoxicity, and free radical neurotoxicity.

Abstract: The present invention provides a new of sulfasalazine as a potent agent for the treatment of neuronal death.

Abstract: This invention provides cells containing recombinant polynucleotides coding for cell surface molecules that, when expressed in the cell, result in rejection of the cell by the host immune system. The invention also provides methods of using such cells, and capsules for delivery of biologically active molecules to a patient.

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 means for obtaining efficient introduction of exogenous genes into a patient, with long term expression of the gene, is disclosed. The gene, under control of an appropriate promoter for expression in a particular cell type, is encapsulated or dispersed with a biocompatible, preferably biodegradable polymeric matrix, where the gene is able to diffuse out of the matrix over an extended period of time, for example, a period of three to twelve months or longer. The matrix is preferably in the form of a microparticle such as a microsphere (where the gene is dispersed throughout a solid polymeric matrix) or microcapsule (gene is stored in the core of a polymeric shell), a film, an implant, or a coating on a device such as a stent. The size and composition of the polymeric device is selected to result in favorable release kinetics in tissue.

Abstract: The invention provides a method for delivering biologically active molecules to the eye by implanting biocompatible capsules containing a cellular source of the biologically active molecule. Also provided is a method of treating ophthalmic diseases using biocompatible capsules.

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: ARPE-19 cells were evaluated as a platform cell line for encapsulated and un-encapsulated cell-based delivery technology. ARPE-19 cells were found to be hardy (the cell line is viable under stringent conditions, such as in central nervous system or intra-ocular environment); can be genetically modified to secrete the protein of choice; has a long life span; is of human origin; has good in vivo device viability; delivers efficacious quantity of growth factor; triggers no or low level host immune reaction, and is non-tumorigenic.

Abstract: 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.

Abstract: An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual.

Abstract: A device is prepared having cells or tissue attached to a non-degradable filamentous matrix surrounded by a semi-permeable membrane. The matrix is preferably formed of a plurality of monofilaments twisted into a yarn or woven into a mesh, and can be in the form of a cylinder. When implanting the device, the semi-permeable membrane is preferably immunolsolatory, and the cells or tissue may produce a biologically active molecule to provide therapy. To enhance cell or tissue adhesion, the matrix is coated with extracellular matrix molecules or treated to provide a surface charge. The device can be made by inserting the matrix into a capsule formed of the semi-permeable membrane, distributing the cells or tissue on the matrix through an opening of the capsule, and sealing the opening of the capsule.

Abstract: A method and device for delivering a biologically active molecule to the eye, either intraocularly or periocularly, and method and device for treating ophthalmic disorders in a patient suffering therefrom.

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: A means for obtaining efficient introduction of exogenous genes into a patient, with long term expression of the gene, is disclosed. The gene, under control of an appropriate promoter for expression in a particular cell type, is encapsulated or dispersed with a biocompatible, preferably biodegradable polymeric matrix, where the gene is able to diffuse out of the matrix over an extended period of time, for example, a period of three to twelve months or longer. The matrix is preferably in the form of a microparticle such as a microsphere (where the gene is dispersed throughout a solid polymeric matrix) or microcapsule (gene is stored in the core of a polymeric shell), a film, an implant, or a coating on a device such as a stent. The size and composition of the polymeric device is selected to result in favorable release kinetics in tissue.

Abstract: This invention is directed to methods of manufacturing implantable biocompatible cell encapsulation devices, wherein the cell encapsulation devices have a jacket made of a permeable, biocompatible material that is loaded with a core made of a reticulate foam scaffold having interconnected pores, with cells that are dispersed in the interconnected pores.

Abstract: This invention provides cells containing recombinant polynucleotides coding for cell surface molecules that, when expressed in the cell, result in rejection of the cell by the host immune system. The invention also provides methods of using such cells, and capsules for delivery of biologically active molecules to a patient.

Abstract: This invention provides cells containing recombinant polynucleotides coding for cell surface molecules that, when expressed in the cell, result in rejection of the cell by the host immune system. The invention also provides methods of using such cells, and capsules for delivery of biologically active molecules to a patient.

Abstract: The invention features immortalized retina-derived (retinal endothelial or retinal epithelial pigmentary) cell lines capable of being implanted in the retina and of carrying a therapeutic substance to the eye and to the central nervous system. Such lines can also be used as a model for studying blood central nervous system interfaces. These lines are derived from primary retinal cultures selected from the group consisting of primary retinal endothelial cells and primary retinal epithelial cells, comprise a nucleic acid fragment containing at least one immortalizing fragment of a heat-sensitive viral oncogene, which nucleic fragment is optionally associated with at least one selection gene, and have the morphological characteristics and at least the expression characteristics of the surface antigens of corresponding primary cultures.

Abstract: A permselective graft polymer is disclosed that is formed by converting into intermediate reactive sites a portion of the cyano groups of a backbone polymer containing —CH2—CH(—C≡N)— units, and grafting polyalkylene oxide polymer chains to the backbone polymer through the reactive sites. Either the backbone polymer of a polymer resin or a permselective polymer membrane can be grafted. When a resin is used, it is formed into a permselective polymer membrane using known methods. The resulting permselective membrane can be formed into hollow fibers or flat sheets for the encapsulation of living cells. The encapsulated cells are then implanted into a patient in need of the biologically active factors produced by the cells. The permselective graft polymer membrane exhibits good molecular diffusion with minimal protein adsorption.

Abstract: A bioartificial extracellular matrix for use in tissue regeneration or replacement is provided by derivatizing a three-dimensional hydrogel matrix with a cell adhesive extracellular matrix protein or cell adhesive peptide fragment of the protein. Preferably, derivatizing is by covalent immobilization of a cell adhesive peptide fragment having the amino acid sequence, ArgGlyAsp, TyrIleGlySerArg or IleLysValAlaVal. Cartilage or tendon can be regenerated by implanting a matrix containing an adhesive peptide fragment that favors 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 pore radius between 120 nm and 290 nm is preferred.