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. The vehicle is particularly well-suited to delivery of insulin from immunoisolated islets of Langerhans, and can also be used advantageously for delivery of high molecular weight products, such as products larger than IgG. A method of making a biocompatible, immunoisolatory implantable vehicle, consisting in a first embodiment of a coextrusion process, and in a second embodiment of a stepwise process.

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. The vehicle is particularly well-suited to delivery of insulin from immunoisolated islets of Langerhans, and can also be used advantageously for delivery of high molecular weight products, such as products larger than IgG. A method of making a biocompatible, immunoisolatory implantable vehicle, consisting in a first embodiment of a coextrusion process, and in a second embodiment of a stepwise process.

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. The vehicle is particularly well-suited to delivery of insulin from immunoisolated islets of Langerhans, and can also be used advantageously for delivery of high molecular weight products, such as products larger than IgG. A method of making a biocompatible, immunoisolatory implantable vehicle, consisting in a first embodiment of a coextrusion process, and in a second embodiment of a stepwise process.

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: 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 method of forming an implantable and retrievable immunoisolatory vehicles is disclosed, the method comprising the steps of first forming a core comprising a volume of at least 1 .mu.l and at least 10.sup.4 cells capable of providing a biologically active product or metabolic or immunologic function, said cells being dispersed in a biocompatible hydrogel or extracellular matrix, and then forming around the core a surrounding external biocompatible thermoplastic or hydrogel jacket free of said cells projecting externally thereof, said jacket having molecular weight cutoff permitting passage of molecules to and from the core through said jacket to provide said biologically active product or function.

Abstract: A method for treatment of a neurodegenerative condition in a patient comprising implanting in the patient at least one immunoisolatory vehicle comprising a corc comprising a volume of at least 1 .mu.l and at least 10.sup.4 living cells which secrete at least one biologically active product, said cells being dispersed in a biocompatible matrix comprising a hydrogel or extracellular matrix components, and an external jacket surrounding the core, the jacket comprising a biocompatible hydrogel or thermoplastic, the jacket being free of cells projecting externally thereof, said jacket having a molecular weight cutoff permitting the passage of the biologically active product from the core through the jacket.

Abstract: A method for treating diabetes in a patient comprising subcutaneously implanting in the patient at least one immunoisolatory vehicle comprising a core comprising a volume of at least 1 .mu.l and at least about 10.sup.4 living cells which secrete insulin, said cells being dispersed in a biocompatible matrix comprising a hydrogel or extracellular matrix components, and a surrounding external jacket of a biocompatible thermoplastic or hydrogel free of said cells projecting externally thereof, said jacket being permselective and immunoisolatory, said jacket having a molecular weight cutoff permitting passage of molecules between the patient and core through said jacket wherein the insulin is released from the immunoisolatory vehicle into the patient's body to treat diabetes.

Abstract: A method of forming an implantable and retrievable immunoisolatory vehicle is disclosed, the method comprising the steps of first forming a jacket of biocompatible thermoplastic or hydrogel, and then loading the jacket with a core comprising a volume of at least 1 .mu.l and at least 10.sup.4 cells capable of secreting a biocompatible matrix comprising a hydrogel or extracellular matrix, said jacket having a molecular weight cutoff permitting passage of molecules thereacross to provide said biologically active product or said function.

Abstract: Immunoisolatory vehicles having a core and a surrounding jacket are disclosed, the core having a volume in excess of 1 .mu.l and at least about 10.sup.4 living cells capable of secreting a biologically active product or of providing a biological function to a patient, the cells dispersed in a biocompatible matrix formed of a hydrogel or an extracellular matrix component, and the external jacket being permselective, biocompatible and having a molecular weight cutoff permitting passage of molecules between the patient and the core through said jacket to provide said biological product or function.

Abstract: A method of making an immunoisolatory vehicle comprised of a core comprising living cells dispersed in a biocompatible matrix is disclosed, the cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function to an individual, and an external jacket surrounding said core which is a biocompatible, permselective thermoplastic or hydrogel, said jacket being free of said cells, comprising coextruding a suspension comprising said cells dispersed in a precursor matrix material comprising extracellular matrix components or a biocompatible hydrogel precursor, and a solution of a biocompatible jacket precursor from a nested dual-bore extrusion nozzle, wherein the suspension of (a) is coextruded from the inner bore and the solution of (b) is coextruded from the outer bore of the nozzle, to form said jacket as the solution of (b) and the suspension of (a) arc coextruded; and exposing the vehicle to a treatment that forms a core comprising a volume of at least 1 .mu.

Abstract: A method of providing a biologically active molecule or metabolic or immunologic function to a patient, comprising implanting into the body of the patient at least one immunoisolatory vehicle comprising a core comprising a volume in excess of 1 .mu.l and at least about 10.sup.4 living cells dispersed in a biocompatible matrix formed of a hydrogel or extracellular matrix components, said cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function to the patient; and an external jacket surrounding said core, said jacket being formed from a thermoplastic or hydrogel, said jacket being free of said cells projecting externally therefrom, said jacket being biocompatible and having a molecular weight cutoff permitting passage of molecules between the patient and the core through said jacket to provide said biologically active product of function.

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: A biocompatible capsule for containing cells for implantation is prepared containing an inner support that provides tensile strength to the capsule. Cells within the capsule are suspended in a liquid medium or immobilized in a hydrogel or extracellular matrix material, and are surrounded by a semipermeable membrane across which biologically active molecules can be delivered from the capsule to surroundings or from the surroundings into the capsule. The inner support may be formed as an integral part of the capsule during a coextrusion process to form the capsule. Alternatively, the inner support may be a discrete component within a tube having top and bottom sealing fittings that are linked withing the tube by the support. 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: A line of .beta. cells is described which is capable of maintaining high levels of insulin secretion in culture. Such cells are useful in the treatment of diabetes, for example, by encapsulation of the cells in an insulin-permeable membrane device, followed by implantation into a diabetes patient.

Abstract: A cell culture of correctly regulated .beta.-cells having enhanced secretion of insulin is described. A method of selecting such correctly regulated .beta.-cells is also described comprising the following steps:(a) providing a population of cells comprising .beta.-cells in which increased intracellular concentrations of calcium ions is correlated with the extracellular presence of glucose;(b) exposing the population to a vital calcium-activated labelling agent;(c) exposing the population to glucose in a concentration sufficient to result in secretion of the insulin; and(d) selecting from the population, cells which exhibit a higher level of intracellular free calcium or insulin secretion when exposed to said concentration.

Abstract: A method of selecting cells with enhanced secretion of a secretory product is disclosed. The method comprises exposing a population of cells to a secretagogue to result in the secretion of a secretory product from the cells and selecting from the population, cells that exhibit increased amounts of intracellular free calcium when exposed to the secretagogue. The method enables the selection of correctly regulated .beta. cells that secrete appropriate amounts of insulin in response to varying glucose levels.