Provided is a cell sheet suitable for cartilage repair. The present invention provides a cell sheet for cartilage repair, formed from a culture of cells derived from a cartilage tissue, and the cell sheet is negative for immunostaining using an antibody against type II collagen. The present invention also provides a method for producing a cell sheet for cartilage repair, formed from a culture of cells derived from a cartilage tissue, and the method includes culturing cells derived from a cartilage tissue on a surface of a membrane, where a temperature-responsive polymer is immobilized on the surface, to give the cell sheet. The culturing is stopped before the cell sheet becomes positive for immunostaining using an antibody against type II collagen.

The present invention provides a composition for regenerating nucleus pulposus and a composition for regenerating an intervertebral disc tissue, each comprising fetal cartilage tissue-derived cells and a fetal cartilage tissue-derived extracellular matrix as active ingredients, and a pharmaceutical composition comprising the composition as an active ingredient for preventing or treating a vertebral disease. Simulating features of the nucleus pulposus, such as compression and tensile strength, the composition for regenerating nucleus pulposus can be regenerated into a tissue similar thereto. The composition for regenerating nucleus pulposus can be implanted into an intervertebral disc to restore an injured intervertebral disc tissue. Hence, the pharmaceutical composition comprising same for preventing or treating a vertebral disease can be used as a basic therapeutic agent for a vertebral disease such as a herniated intervertebral disc.

This invention provides disrupted cartilage products, methods of manufacturing disrupted cartilage products, and methods of treating a subject comprising administering a cartilage product. The cartilage products are manufactured by a method comprising disrupting a collagen matrix, e.g. to produce a flexible cartilage product. Optionally, the cartilage products comprise viable chondrocytes, bioactive factors such as chondrogenic factors, and a collagen type II matrix. Optionally, the cartilage products are non-immunogenic.

This invention provides porated cartilage products and methods of producing porated cartilage products. Optionally, the cartilage products are sized, porated, and digested to provide a flexible cartilage product. Optionally, the cartilage products comprise viable chondrocytes, bioactive factors such as chondrogenic factors, and a collagen type II matrix. Optionally, the cartilage products are non-immunogenic.

A method of modulating transdifferentiation of chondrocytes to osteoblast includes administering to the chondrocytes an agent that modulates GP130 receptor signaling and expression of at least one of Sox2, Oct4, or Nanog of the chondrocytes.

The present application is directed to a method of treating osteoarthritis, which includes obtaining a member of a transforming growth factor superfamily of proteins; obtaining a population of cultured mammalian cells that may contain vector encoding a gene, or a population of cultured connective tissue cells that do not contain any vector encoding a gene; and then transferring the protein and the connective tissue cells into an arthritic joint space of a mammalian host, such that the activity of the combination within the joint space results in regenerating connective tissue.

A method for preparing zonal layered chondrocyte sheets, comprising the steps: (a) providing a cartilage sample from a subject; (b) isolating chondrocytes from the cartilage sample and then isolating superficial zone chondrocytes, middle zone chondrocytes and deep zone chondrocytes from the chondrocytes; (c) culturing the deep zone chondrocytes until reaching 100% cell confluence to form a deep zone chondrocyte sheet; (d) seeding the middle zone chondrocytes on the top of the cultured deep zone chondrocyte sheet from the step (c) and culturing the middle zone chondrocytes until reaching 100% cell confluence to form a middle zone chondrocyte sheet; and (e) seeding the superficial zone chondrocytes on the top of the cultured middle zone chondrocyte sheet from the step (d) and culturing the superficial zone chondrocytes until reaching 100% cell confluence to form a superficial zone chondrocyte sheet to obtain the zonal layered chondrocyte sheets.

A graft or construct including an isolated cartilage chondrocytes from young donors (<20 years), seeded on a three-dimensional membrane composed of one of the main chondrogenesis-promoting substances (hyaluronic acid), in high densities (1×106) with autologous serum and sealed with a fibrin adhesive for the treatment of a cartilage lesion, with tissue formation that has greater durability, at a lower cost and with fewer risks than the treatments currently available for the management of such lesions. Likewise, a procedure for the treatment of articular cartilage lesions is provided, through the implantation of allogeneic chondrocyte grafts that present the capacity to generate or repair satisfactorily the cartilage of the lesion.

The subject invention is directed to a mixed cell composition to generate a therapeutic protein at a target site by providing a first population of mammalian cells transfected or transduced with a gene that is sought to be expressed, and a second population of mammalian cells that have not been transfected or transduced with the gene, wherein endogenously existing forms of the second population of mammalian cells are decreased at the target site, and wherein generation of the therapeutic protein by the first population of mammalian cells at the target site stimulates the second population cells to induce a therapeutic effect.

A modular engineered tissue construct includes a plurality of fused self-assembled, scaffold-free, high-density cell aggregates. At least one cell aggregate includes a plurality of cells and a plurality of biocompatible and biodegradable nanoparticles and/or microparticles that are incorporated within the cell aggregates. The nanoparticles and/or microparticles acting as a bulking agent within the cell aggregate to increase the cell aggregate size and/or thickness and improve the mechanical properties of the cell aggregate as well as to deliver bioactive agents.