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 invention covers a method of implanting a living donor cell into a host animal without inflammatory response or rejection of the donor cell by the host animal, by obtaining an uncoated particle of a biocompatible, temperature-independent gel that encapsulates the living donor cell, wherein the uncoated particle provides a molecular weight cutoff that prevents host animal immune cells from entering the particle, yet does not have to prevent entry of host animal IgG and complement into the particle, and implanting the uncoated particle into the host animal.

Abstract: Elongated seamless capsules containing biological material are prepared by a method in which a coagulant, which includes a cell suspension or other biological material, and a polymeric casting solution are extruded through a common extrusion port having at least two concentric bores, such that the coagulant is extruded through an inner bore and the polymeric casting solution is extruded through an outer bore. Extrusion of the coagulant is initiated subsequent to initiating delivery of the casting solution to form a capsule having a curved and smooth leading edge shape. Delivery of the coagulant is then shut off, and extrusion of the casting solution is terminated either immediately or after some predetermined time. This procedure can be modified to form in the capsule a coaxial rod that is connected to one end but not the other end of the capsule.

Abstract: A coating apparatus includes a rotary cup for forming beads and projecting them radially outwardly, and one or more collection basins surrounding the bead forming cup. The cup is adjustably rotatable about its central axis, and the collection basins are independently rotatable and positioned to collect the beads projected from the cup. The coating apparatus further includes an elevation adjustment system for axially adjusting the alignment of the cup with respect to the selected collection basins. The rotational speeds of the cup and the collection basins are selected so as to minimize the impact of the beads against a gelling solution in the collection basins. In use, a supply mixture is introduced into a mixing chamber of the cup. As the cup spins, the coated particles are propelled upwardly by the centrifugal force from the mixing chamber along the inner surface of the cup, and are projected radially outwardly, as beads, into the gelling solution in one of the selected basins.

Abstract: Biological agents such as secretory cells are encapsulated in a hydrophilic gel made of agarose or collagen-agarose and gelatin sponge-agarose combinations. In a preferred embodiment, semi-solid beads are formed from a suspension containing collagen, agarose and secretory cells such as pancreatic islets, the collagen is polymerized to form solid, agarose-collagen beads and the solid beads are coated with agarose. Coating is preferably by rolling the solid beads in about 5-10% agarose, contacting the rolled beads with mineral oil and washing oil from the beads. Beads containing secretory cells can be transplanted into a mammal to treat a condition caused by impaired secretory cell function.

Abstract: A method for maintaining hepatocytes in culture includes providing the hepatocytes with a support, the support including extracellular matrix, the support having a configuration that permits each of at least a portion of the hepatocytes to form at least one apical surface and at least two discrete basal surfaces.