Chondrocyte-like cells useful for tissue engineering and methods
AssigneeThe Regents of the University of California
InventorsRajendra S. Bhatnagar, Steven B. Nicoll
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Abstract
Fibroblast cells are treated with a chemical inhibitor of protein kinase C such as staurosporine, in conjunction with functionally hypoxic micromass culture so as to be induced into chondrogenic differentiation. Such fibroblast-derived, chondrocyte-like cells may be seeded onto three-dimensional polymer scaffolds for use in the repair of articular cartilage lesions, and thus can obviate the need for invasive techniques to harvest autologous chondrocytes from a limited supply of existing articular cartilage, or to avoid the need for obtaining allogeneic chondrocytes from non-biocompatible donor tissues.
Claims14
A method for producing cells with a chondrocyte phenotype, useful for autogenous tissue repair, comprising:
- obtaining fibroblasts derived from the dermis of an intended patient;
- and
- culturing the fibroblasts in a state of hypoxia and in the presence of at least one agent that promotes differentiation along a chondrogenic pathway;
- wherein said culturing provides for conversion of the fibroblasts to display a chondrocyte phenotype even in the absence of exogenously added growth factor, the chondrocyte phenotype being selected from the group consisting of production of type II collagen with down-regulation of type I collagen, expression of aggrecan and type II collagen mRNA with down-regulation of type I collagen, chrondrocyte cellular morphology, and production of at least one cartilage matrix component.
A cartilage repair composition, comprising:
- a matrix;
- and,
- cells displaying a chondrocyte phenotype seeded on the matrix, the cells being derived from non-chondrocytes cultured in a state of hypoxia and in the presence of at least one agent that promotes differentiation along a chondrogenic pathway even in the absence of exogenously added growth factors.
A tissue repair composition, comprising:
- a high density micromass of non-chondrocyte cells in a synthetic media, wherein the non-chondrocyte cells are in a state of hypoxia and the media includes at least one agent that promotes differentiation along a chondrogenic pathway, said state of hypoxia and said agent producing a chondrocyte phenotype in the non-chondrocyte cells even in the absence of exogenously added growth factors.
An isolated cell culture composition, comprising:
- non-chondrocyte cells displaying a chondrocyte phenotype in a cell culture medium, the cell culture medium comprising a hypoxia-inducing agent and at least one agent which promotes differentiation along a chondrogenic pathway even in the absence of exogenously added growth factors.
Dependencies are inferred from the claim text.