North Shore-long Island Jewish Research Institute

The Feinstein Institute for Medical Research

North Shore University Hospital Research Corporation

James M Mason

Daniel A Grande

Arnold S Breitbart

Siamak Tabibzadeh

Daniel S Grande

Provided are tissue scaffolds colonized by vertebrate cells expressing, a transgenic bioactive molecule, where the vertebrate cells are unable to undergo mitosis. Also provided are methods of growing tissue in a mammal and methods of delivering a transgenic bioactive molecule to a tissue of a mammal, using the tissue scaffolds. Additionally, methods of making the tissue scaffolds are provided.

Bioactive scaffolds

Provided are tissue scaffolds colonized by vertebrate cells expressing a transgenic bioactive molecule, where the vertebrate cells are unable to undergo mitosis. Also provided are methods of growing tissue in a mammal and methods of delivering a transgenic bioactive molecule to a tissue of a mammal, using the tissue scaffolds. Additionally, methods of making the tissue scaffolds are provided.

The present invention relates to the use of non-primate mammalian cell lines having substantially no endogenous retroviral sequences as producer and packaging lines for preparation of human serum-resistant retroviral vector particles with improved safety for use in gene therapy applications. In a preferred embodiment, the cell line used in the present invention is the &agr;-galactosyl (&agr;Gal)-positive cell ferret brain cell line designated as Mpf or a cell line having those identifying characteristics of the Mpf cell line suitable for the practice of the invention.

Use of human serum resistant vector particles and cell lines for human gene therapy

The present invention provides a method for inhibiting activity of TGF-&bgr;, comprising contacting tissue expressing TGF-&bgr; with an amount of ebaf or an ebaf analogue. The present invention further provides a method for treating a condition associated with overactivity of TGF-&bgr;, particularly fibrosis, a defect in cell proliferation, or a coagulation defect. The present invention also provides a method for inhibiting activity of TGF-&bgr;, comprising contacting tissue expressing TGF-&bgr; with a modulator of ebaf expression, or a modulator of expression of an ebaf analogue. The present invention is further directed to a method for treating fibrosis in a subject in need of treatment, comprising administering to the subject an amount of ebaf or an ebaf analogue effective to treat the fibrosis. Finally, the present invention provides a method for treating a defect in cell proliferation in a subject in need of treatment, comprising administering to the subject an amount of ebaf or an ebaf analogue effective to treat the defect in cell proliferation.

Inhibition of TGF-&bgr; and uses thereof

A method for enhancing and/or increasing the efficiency of repair of tissues, primarily bone or cartilage, using genetically engineered cells has been developed. In the preferred embodiment, mesenchymal stem cells are isolated from periosteum tissue, and transfected with the gene encoding a growth factor for the particular cell type to be repaired. For example, for repair of bone, a gene (or genes) encoding bone morphogenic protein is transfected into periosteal cells. The transfected periosteal cells then express the bone morphogenic protein in culture to promote bone repair as a function of the expressed bone morphogenic protein. Cells can be transfected using any appropriate means, including viral vectors, as shown by the example, chemical transfectants, or physico-mechanical methods such as electroporation and direct diffusion of DNA. Genes can encode any useful protein, for example, a specific growth factor, morphogenesis factor, a structural protein, or a cytokine which enhances the temporal sequence of wound repair, alters the rate of proliferation, increases the metabolic synthesis of extracellular matrix proteins, or directs phenotypic expression in endogenous cell populations. Representative genes encoding proteins include bone growth factor genes, cartilage growth factor genes, nerve growth factor genes, and general growth factors important in wound healing, such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), epidermal growth factor (EGF), basic fibroblast growth factor (FGF), endothelial derived growth supplement.

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Bethpage, NY, United States of America

James M Mason