Abstract: The disclosure describes engineered cells for the treatment of joint and bone disease. The cells are engineered to sense signals only found in diseased compartments and in turn produce therapeutic molecules that are secreted into the local environment.

Abstract: Provided are methods and compositions to target delivery of cells to a tissue lesion, thereby treating the lesion. For example, biotinylated antibodies with affinity to a lesion epitope are administered at the lesion. Reparative cells including avidin and biotin are then administered at the lesion. The reparative cells are targeted to the lesion via avidin-biotin bridges to the antibodies, with additional cells recruited to the lesion via cell-to-cell avidin-biotin bridges. In certain examples, antibody-reparative cell complexes are formed by mixing the biotinylated antibodies with the reparative cells including avidin and biotin. The complexes are then administered at the lesion. In other examples, multivalent antibodies are used to target reparative cells to the lesion, such as by binding an epitope at the lesion and an epitope present on the reparative cell. In other examples, the antibodies are chemically linked to a reparative cell or to a nanosome containing a therapeutic agent.

Abstract: Matrix metalloproteinases are major mediators of tissue destruction in various chronic inflammatory disorders. The present invention demonstrates that over-expression of intracellular isoform of IL-1 receptor antagonist confers to recipient cells resistance to signaling pathways of proinflammatory cytokines (such as tumor necrosis factor alpha and IL-1 beta) that induce matrix metalloproteinase and subsequent tissue degradation. Hence, over-expression of intracellular IL-1 receptor antagonist may inhibit tissue destruction in various inflammatory disorders such as rheumatoid arthritis, other arthritides, degenerative intervertebral disc disease and chronic skin ulcers that occurs in diabetes mellitus and bed-ridden patients.

Abstract: Matrix metalloproteinases are major mediators of tissue destruction in various chronic inflammatory disorders. The present invention demonstrates that over-expression of intracellular isoform of IL-1 receptor antagonist confers to recipient cells resistance to signaling pathways of proinflammatory cytokines (such as tumor necrosis factor alpha and IL-1 beta) that induce matrix metalloproteinase and subsequent tissue degradation. Hence, over-expression of intracellular IL-1 receptor antagonist may inhibit tissue destruction in various inflammatory disorders such as rheumatoid arthritis, other arthritides, degenerative intervertebral disc disease and chronic skin ulcers that occurs in diabetes mellitus and bed-ridden patients.

Abstract: Matrix metalloproteinases are major mediators of tissue destruction in various chronic inflammatory disorders. The present invention demonstrates that over- expression of intracellular isoform of IL-1 receptor antagonist confers to recipient cells resistance to signaling pathways of proinflammatory cytokines (such as tumor necrosis factor alpha and IL-1 beta) that induce matrix metalloproteinase and subsequent tissue degradation. Hence, over-expression of intracellular IL-1 receptor antagonist may inhibit tissue destruction in various inflammatory disorders such as rheumatoid arthritis, other arthritides, degenerative intervertebral disc disease and chronic skin ulcers that occurs in diabetes mellitus and bed-ridden patients.

Abstract: Matrix metalloproteinases are major mediators of tissue destruction in various chronic inflammatory disorders. The present invention demonstrates that over-expression of intracellular isoform of IL-1 receptor antagonist confers to recipient cells resistance to signaling pathways of proinflammatory cytokines (such as tumor necrosis factor alpha and IL-1 beta) that induce matrix metalloproteinase and subsequent tissue degradation. Hence, over-expression of intracellular IL-1 receptor antagonist may inhibit tissue destruction in various inflammatory disorders such as rheumatoid arthritis, other arthritides, degenerative intervertebral disc disease and chronic skin ulcers that occurs in diabetes mellitus and bed-ridden patients.