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Genetic engineering of cells to enhance healing and tissue regeneration
| Details |
Inventors: Breitbart, Arnold S.; Grande, Daniel S.; Mason, James M.;
Assignee: North Shore-Long Island Jewish Research Institute (Manhasset, NY)
Primary Examiner: Yu; Mickey
Assistant Examiner: Nguyen; Tram A.
Attorney, Agent or Firm: Arnall Golden & Gregory, LLP
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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DETAILED DESCRIPTION OF THE INVENTION It has been discovered that cells can be genetically engineered to produce bioactive molecules which act on the cells that are expressing the molecules, or cells adjacent to or in physiological contact with the genetically engineered cells, to alter their growth, differentiation, and/or efficiency of development into new tissue, thereby either promoting wound healing or formation of new tissue.
The finding was made empirically, using mesenchymal cells obtained from periosteum, which were then genetically engineered to express bone morphogenic protein ("BMP").
Possible results could have included feedback inhibition of expression, lack of controlled, normal development, or transient expression of only limited benefit.
The actual results obtained show that the cells continue to express the BMP after implantation of the genetically engineered cells, and that the BMP is active on the cells.
These results are predictive of results obtained with other cell types and bioactive molecules.
I.
Cells.
The cells that can be manipulated for use in the methods described herein include almost any type of tissue.
These are typically normal mammalian cells, preferably of the same species as the ultimate recipient, most preferably of the same origin as the recipient, although the method can be practiced using xenotransplants which have been altered to decrease the liklihood of rejection, for example, by expression of a complement inhibitor such as CD59, or masking of sugar residues.
These techniques are known to those skilled in the art, and have been commercially developed using pigs as the donors, by Alexion Pharmaceuticals, Conn.
, and DNX, PA.
Cell type will typically be selected based on the tissue to be repaired or formed.
For example, chondrocytes or fibroblasts can be selected to form cartilage; muscle cells to form muscle.
Undifferentiated, or less differentiated, cells may be preferred in some situation.
Representative of these cell types include stem cells and mesenchymal cells
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Gene Therapy 
