Patch graft compositions for cell engraftment

Abstract

Compositions and methods of transplanting cells by grafting strategies into solid organs (especially internal organs) are provided. These methods and compositions can be used to repair diseased organs or to establish models of disease states in experimental hosts. The method involves attachment onto the surface of a tissue or organ, a patch graft, a “bandaid-like” covering, containing epithelial cells with supporting early lineage stage mesenchymal cells. The cells are incorporated into soft gel-forming biomaterials prepared under serum-free, defined conditions comprised of nutrients, lipids, vitamins, and regulatory signals that collectively support stemness of the donor cells. The graft is covered with a biodegradable, biocompatible, bioresorbable backing used to affix the graft to the target site. The cells in the graft migrate into and throughout the tissue such that within a couple of weeks they are uniformly dispersed within the recipient (host) tissue. The mechanisms by which engraftment and integration of donor cells into the organ or tissue involve multiple membrane-associated and secreted forms of MMPs.

1 - 26 . (canceled) 
     
     
         27 . A covering or coating for a patch graft or tissue, comprising a hydrogel or other biomaterial with sufficient viscoelasticity and resilience to withstand mechanical forces, including such forces from other tissues and organs. 
     
     
         28 . The covering or coating for a patch graft or tissue of  claim 27 , wherein the hydrogel comprises one or more hyaluronans. 
     
     
         29 . The covering or coating for a patch graft or tissue of  claim 27 , wherein the hydrogel has a viscoelasticity from about 250 to 500 Pa. 
     
     
         30 . The covering or coating for a patch graft or tissue of  claim 27 , wherein the hydrogel has a viscoelasticity from about 250 Pa to about 350 Pa. 
     
     
         31 . The covering or coating for a patch graft or tissue of  claim 27 , wherein the patch graft or tissue is engrafted to a target organ, and wherein the mechanical forces are exerted by tissues and organs adjacent to the target organ. 
     
     
         32 . The covering or coating for a patch graft or tissue of  claim 31 , wherein the target organ is selected from the group consisting of liver, pancreas, biliary tree, thyroid, thymus thymus, intestines, lung, prostate, breast, brain, spinal cord, neural ganglia, skin and underlying dermal tissues, uterus, bone, tendon, cartilage, kidney, muscle, blood vessels, or heart.