• 1) "Acute rejection is generally acknowledged to be mediated by T cell responses to proteins from the donor organ which differ from those found in the recipient. Unlike antibody-mediated hyperacute rejection, development of T-cell responses first occurs several days after a transplant if the patient is not taking immunosuppressant drugs. Since the development of powerful immunosuppressive drugs such as cyclosporin, tacrolimus and rapamycin, the incidence of acute rejection has been greatly decreased, however, organ transplant recipients can develop acute rejection episodes months to years after transplantation. Acute rejection episodes can destroy the transplant if it is not recognized and treated appropriately. Episodes occur in around 60-75% of first kidney transplants, and 50 to 60% of liver transplants. A single episode is not a cause for concern if recognised and treated promptly and rarely leads to organ failure, but recurrent episodes are associated with chronic rejection of grafts. The bulk of the immune system response is to the Major Histocompatibility Complex (MHC) proteins. MHC proteins are involved in the presentation of foreign antigens to T-cells, and receptors on the surface of the T-cell (TCR) are uniquely suited to recognition of proteins of this type. MHC are highly variable between individuals, and therefore the T-cells from the host recognize the foreign MHC with a very high frequency leading to powerful immune responses that cause rejection of transplanted tissue. Identical twins and cloned tissue are MHC matched, and are therefore not subject to T-cell mediated rejection. The first successful organ transplant was performed between identical twins by Dr. Joseph Murray at the Peter Bent Brigham Hospital in Boston. This transplant was successful because no T-cell mediated responses were generated to the transplanted organ. Dr. Murray later received a Nobel prize for his work." Source and further information: 2) "Coagulation proteases are involved in generating fibrin after vascular injury (hemostasis) but they also have multiple other effects, many of which are mediated independently of fibrin generation, via interactions with specific cell membrane-expressed ‘protease activated receptors’. In inflammation, this family of proteins has a complex influence, the facets of which are still incompletely understood, though a common feature in different models appears to be amplification of innate signals that are initially generated by pathogenic elements or, in the context of transplantation, ischemia or anti-graft antibodies, for instance. There is increasing evidence that these proteases may also have specific effects on cells involved in adaptive immunity and on cells that mediate chronic inflammation and fibrosis. Understanding whether these effects are relevant in the responses generated against transplanted organs is important, as it could lead ultimately to the development of novel ways to promote long-term graft survival." Source and further information: 3) "That experiment was enough to convince Rubinsky that sugar might be the key to freezing rat livers. So a few years ago, he perfused fresh rat livers with the fish antifreeze protein and glycerol, and then froze them. Glycerol has similar antifreeze and anti-dehydration properties to glucose but it has smaller molecules which cross cell membranes more easily. After six hours, the rat livers, which were thawed and washed to remove the glycerol, could still produce bile in a culture dish. Now, with money from A/F Protein in Waltham, Massachusetts, a company Rubinsky co-founded to commercialise naturally occurring antifreeze proteins, he's getting ready to transplant freshly thawed livers back into live rats. If he succeeds, it will be a first for cryogenics." Source and further information: Further information: 4) "The present invention relates to media comprising purified antimicrobial peptides, pore forming agents, and/or cell surface receptor binding compounds and their use for the storage and preservation of organs prior to transplant. " "The present invention relates to media comprising antimicrobial polypeptides or pore forming agents and/or cell surface receptor binding compounds and their use for the storage and preservation of organs prior to transplant." Source and further information:

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