Graft survival

Contamination of blood products with lymphocytes can lead to transfusion-induced reactions ranging from a mild fever to severe reactions such as alloimmunization and graft versus host disease (GvHD), in which the transfused lymphocytes (graft) survive the defensive immune reaction of the patient (host) and start a reaction which destroys the cells of the host. The patient also may develop an immune response to the human leukocyte antigen (HLA) type of the graft s cells and reject all platelet transfusions that do not match their own HLA system. The HLA system, found on blood platelets and lymphocytes, is more compHcated than, but similar to, the ABO blood group system of red cells. 

The goals of maintenance immunosuppression are to further aid in preventing acute rejection episodes and to optimize patient and graft survival Anti-rejection medications require careful selection and dosage titration to balance the risks of rejection with the risks of adverse events. Common maintenance immunosuppressive agents can be divided into four basic medication classes ... 

Successful outcomes in solid-organ transplantation generally are measured in terms of several separate end points (1) preventing acute rejection (2) increasing 1-year graft survival ... 

Vassalli G, Simeoni E, Li JP, Fleury S. Lentiviral gene transfer of the chemokine antagonist RANTES 9-68 prolongs heart graft survival. Transplantation 2006 81 240-246. 

Teramura Y, Iwata H (2011) Improvement of graft survival by surface modification with poly (ethylene glycol)-lipid and urokinase in intraportal islet transplantation. Transplantation 91 271-278... 

Teramura Y, Iwata H (2009) Surface modification of islets with PEG-lipid for improvement of graft survival in intraportal transplantation. Transplantation 88 624-630... 

Although ciclosporin and tacrolimus applied systemically improve psoriatic lesions, they are clearly less active when applied topically. Therefore, liposomal preparations have been developed. Indeed, ciclosporin penetrates deeper strata of rodent and human cadaver skin more efficiently when incorporated into liposomes [51], Moreover, tacrolimus concentrations in murine skin have increased ninefold, and skin graft survival prolonged, if the drug is liposome encapsulated [52]. This indicates that topical psoriasis therapy with tacrolimus may become possible. At present, topical tacrolimus is confined to the less recalcitrant forms of mild eczema. 

Knight SR, Russell NK, Barcena L, Morris PJ. (2009) Mycophenolate mofetil decreases acute rejection and may improve graft survival in renal transplant recipients when compared with azathioprine A systematic review. Transplantation 87 785-794. 

Results of our experiments suggest that (1) dermal substitute biomaterials may contribute to the improved wound re-epithehalisation when combined with cultured autologous keratinocytes and (2) porcine collagen paste is able to support splitthickness skin graft survival as well as autologous cultured keratinocyte proliferation. 

F. Role in therapy In the setting of renal transplantation, Zenapax, administered prophylactically may improve graft survival and mortality when added to standard immunosuppressive regimens. 

E. Therapeutic response The safety and efficacy of Simulect, when added to a standard immunosuppressive regimen comprised of cyclosporine and corticosteroids, were assessed in two placebo-controlled trials. The primary end point in both studies was the incidence of death, graft loss, or an episode of acute rejection during the first 6 months post-transplantation. Patients receiving Simulect experienced a significantly lower incidence of biopsy-confirmed rejection episodes at both 6 and 12 months after transplantation, but there was no difference in the rate of delayed graft function, patient survival, or graft survival between Simulect-treated patients and placebo-treated patients in either study. 

The introduction of cyclosporin, a peptide derived from a fungus, revolutionised immunosuppressive therapy, and was one of the major influences in the improvement of early graft survival in transplant surgery when introduced in the 1980s. The main action is a relatively selective inhibition of IL-2 production and consequently a decreased proliferation of T cells. A major advantage of cyclosporin is that it does not cause myelosuppression in therapeutic doses. The major side effect is nephrotoxicity, which occurs in about 20% of patients, and about 50% of patients develop moderate hypertension. The other major side effect is hepatotoxicity with cholestasis and hyperbilirubinaemia. 

Bartholomew, A., Sturgeon, C, Siatskas, M., et al. (2002), Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo, Exp. Elematol., 30(1), 42 18. 

Vroemen, M, Aigner, L., Winkler, J., Weidner, N. (2003). Adult neural progenitor cell grafts survive after acute spinal cord injury and integrate along axonal pathways. Eur J Neurosci, 18, 743-51. 

Goncalves LF, Ribeiro AR, Berdichevski R, Joelsons G. 2007. Basiliximab improves graft survival in renal transplant recipients with delayed graft function. Transplant Proc. 39 437 138. 

Tacrolimus + sirolimus, tacrolimus + mycophenolate mofetil, and ciclosporin + sirolimus have been compared in recipients of their first kidney transplant (52). One-year patient and graft survival did not differ. Ciclosporin + sirolimus was associated with increased serum creatinine concentrations, reduced creatinine clearance, more frequent protocol discontinuation, more antihyperlipidemic drug therapy, and a higher incidence of post-transplant diabetes mellitus. 

Transgenic islets Prevention of cytokine-induced apoptosis and prolonged islet graft survival... 

Bottino, R., Fernandez, L. A., Ricordi, C., Lehmann, R., Tsan, M. F., Oliver, R. and Inverardi, L. (1998). Transplantation of allogeneic islets of Langer-hans in the rat liver Effects of macrophage depletion on graft survival and microenvironment activation. Diabetes 47, 316-323. 

Deng, S., Ketchum, R. J., Yang, Z. D., Kucher, T., Weber, M., Shaked, A., Naji, A. and Brayman, K. L. (1997). IL-10 and TGF-beta gene transfer to rodent islets Effect on xenogeneic islet graft survival in naive and B-cell-deficient mice. Transplant Proc. 29, 2207-2208. 

Fujita, J., Zhou, J.-P., Szot, G., Ostrega, D., Baldwin, A., Park, C.-G., Thompson, C., Bluestone, J. and Polonsky, K. (2000). Bcl-xL overexpression prevents cytokine-induced dysfunction and apoptosis in pancreatic b cells and prolongs graft survival in islet transplantation. Diabetes 49 (Abstract). 

Kapturczak, M. H., Flotte, T. and Atkinson, M. A. (2001). Adeno-associated virus (AAV) as a vehicle for therapeutic gene delivery Improvements in vector design and viral production enhance potential to prolong graft survival in pancreatic islet cell transplantation for the reversal of type 1 diabetes. Curr. Mol. Med. 1, 245-258. 

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