Method of preparing transplant tissue to reduce immunogenicity upon implantation
First Claim
1. An in vitro process for generating implants or grafts of collagenous, connective, or vascular tissue which are xenogeneic to a human recipient comprising decellularizing a natural tissue to produce a tissue matrix, the tissue matrix is next washed to remove cellular antigens, or extracellular antigens, or both, followed by treatment of the tissue matrix with adhesion factors comprised of fibronectin and heparin effective to promote attachment thereto of fibroblast cells immunologically acceptable to the implant or graft recipient, next the tissue matrix is treated with adhesion factor and is repopulated by incubating the matrix in the presence of the fibroblast cells and fibroblast growth factor until such cellular repopulation provides a vitalized tissue histologically similar to the corresponding natural tissue, and wherein the implant tissue generated is mechanically, biochemically and immunologically suitable for implantation.
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Abstract
This disclosure includes a method for generating a functional hybrid bioprosthesis. Tissue formed naturally of interstitial collagens is treated to kill native cells and remove potentially immunologically active soluble molecules. Then it may be treated sequentially with extracellular matrix adhesion factor such as fibronectin, extracellular matrix glycosaminoglycan such as heparin, and growth factor appropriate to the cell type required to function within the matrix, and incubating the transplant tissue matrix with cells that are either allogeneic or autologous for the recipient thereby imparting to the matrix the characteristics of the cell type and tissue selected. Tissues with a variety of functional bioactivities can thus be formed in vitro prior to graft transplantation or implantation which will exhibit reduced or no stimulation of an immunological response in the recipient.
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20 Claims
- 1. An in vitro process for generating implants or grafts of collagenous, connective, or vascular tissue which are xenogeneic to a human recipient comprising decellularizing a natural tissue to produce a tissue matrix, the tissue matrix is next washed to remove cellular antigens, or extracellular antigens, or both, followed by treatment of the tissue matrix with adhesion factors comprised of fibronectin and heparin effective to promote attachment thereto of fibroblast cells immunologically acceptable to the implant or graft recipient, next the tissue matrix is treated with adhesion factor and is repopulated by incubating the matrix in the presence of the fibroblast cells and fibroblast growth factor until such cellular repopulation provides a vitalized tissue histologically similar to the corresponding natural tissue, and wherein the implant tissue generated is mechanically, biochemically and immunologically suitable for implantation.
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