Tissue transplantation

The original experiments of tissue transplantation were done by using skin transplants in inbred strains of mice. In 1908, Alexis Carrel first reported kidney transplantation in cats, but all the cats died, and only some exhibited a functional urinary output. George Schone published in 1912 the difficulties associated with tissue transplantation, which were not related to surgery, asepsis and anesthesia. He wrote six laws of tissue transplantation, which to date are accepted  

Immunopharmacology, DOI 10.1007/978-0-387-77976-8.7, Springer Science+Business Media, LLC 2008 

The above-mentioned observations were also described in humans by P.B. Medawar in the 1940s. Based on his observations in humans, and later in animal experiments, he concluded that the graft rejection was a result of immune response, which eventually led to the discovery of MHC. The development of acquired immune response to transplanted tissue results in the rejection of the tissue where cytotoxic T cells, inflammatory T cells and antibodies play a major role in the rejection process. 

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For an allogeneic HCT, the recipient and the donor are dissimilar genetically unless they are identical twins (referred to as a syngeneic HCT). The tissue transplanted is immunologi-cally active, and thus there is potential for bidirectional graft... 

Decontamination Soap and water, or diluted sodium hypochlorite solution (0.5 percent) for environmental contamination. Drainage and secretion procedures are necessary. Standard precautions for healthcare workers should be followed. Person-to-person transmission via tissue transplantation and sexual contact has been reported but are insignificant. 

Direct person-to-person spread of brucellosis is extremely rare. Mothers who are breast-feeding may transmit the infection to their infants. Sexual transmission has also been reported. For both sexual and breast-feeding transmission, if the infant or person at risk is treated for brucellosis, their risk of becoming infected wiil probably be eliminated vwthin 3 days. Although uncommon, transmission may also occur via contaminated tissue transplantation. 

Why would tissue transplanted from father to daughter have a greater risk of being detected as foreign than a tissue transplanted between identical twins ... 

The protein phosphatase calcineurin was of particular interest since it mediates the immunosuppressive effect of the pharmaceuticals cyclosporin and FK506, often used in organ and tissue transplantations. The biochemical point of application of both pharmaceuticals was unclear for a long time. In initial experiments, it was found that cyclosporin and FK506 bind specifically to two proteins known as cyclophilin and FK506 binding protein, respectively. Both proteins function as peptidyl prolyl cis/trans isome-rases (review Fischer, 1994). 

Under the revised system, CBER will continue to review blood products and vaccines. These product areas are CBER s strengths and the basis for creation of the biologies division. CBERwill also be responsible for evaluating gene therapy and tissue transplantation products as the development of these novel entities comes to fruition. 

Experimentation has also been performed in tissue transplantation to replenish the cell lost in PD. Samples of a victim s own adrenal tissue have... 

Establishment of tolerance to tissue grafts. If a newborn X mouse is injected with Y cells when it is young, it is tolerant to Y tissue transplants when it becomes an adult. If the X mouse is not exposed to Y cells at an early age, it readily rejects the tissue graft. 

Cyclosporine is used to prevent organ rejection after tissue transplantation. It is also used for rheumatoid arthritis, psoriasis and dry eyes (keratoconjunctivitis sicca). For... 

Sirolimus is used for tissue transplantation where its major advantage over calci-neurin inhibitors is that it is not nephrotoxic. Chronic renal failure in transplant patients who have taken calcineurin inhibitors for the long term can be prevented by the administration of sirolimus. Steroid-free immunosuppression can be achieved by administering sirolimus alone or in combination with mycophenolate mofetil and cyclosporine or tacrolimus. Since impaired wound healing is one of its potential side effects, some transplant centers use sirolimus only after several weeks of surgery. 

Mycophenolate mofetil is used for tissue transplantation in combination with tacrolimus or cyclosporine or sirolimus plus glucocorticoids. It is used more than any other cytotoxic drug either at the time of the transplant or following the initiation of acute rejection. Mycophenolate mofetil is a prophylactic agent and cannot be used for chronic rejection or ongoing acute rejection. 

Originally developed for chemotherapy, azathioprine is used today mainly as an immunosuppressive agent and rarely as an antineoplastic drug. It was introduced as an immunosuppressive agent by a British pioneer of tissue transplantation, Roy Caine. Azathioprine was used to prevent rejection after tissue transplantation as a replacement for 6-mercaptopurine because it was less toxic. In addition to tissue transplantation, it is also used for rheumatoid arthritis and Crohn s disease. Azathioprine is a prodrug which in the body is converted to its active metabolites 6-mercaptopurine and 6-thioinosinic acid. Until the discovery of cyclosporine, azathioprine in combination with steroids was the standard treatment to prevent rejection after tissue transplantation. 

Azathioprine is administered to patients who do not respond to calcineurin inhibitors, sirolimus and glucocorticoids. Daily doses of 3-10 mg/kg of azathioprine are administered 1 or 2 days before renal transplantation or on the day of surgery for prophylactic therapy. Mycophenolate mofetil is increasingly used in place of azathioprine for tissue transplantation since it is less myelotoxic and causes few opportunistic infections. 

The monoclonal antibodies used as immunosuppressive agents in tissue transplantation include muromonoab-CD3, daclizumab and basiliximab. Muromonoab-CD3 binds to a specific site on CD3 receptors and interferes with the ability of the TCR to bind the antigen and also inhibits CD3 receptor-dependent signal transduction mechanisms, all of which result in immune suppression. Both daclizumab and basiliximab are monoclonal antibodies directed against IL-2 receptors and consequently inhibit IL-2-dependent responses after tissue transplantation, resulting in immune suppression. The monoclonal antibodies used as immunosuppressive agents are described in detail in Chapter 5. 

Daclizumab is used for the prophylaxis of acute rejection in patients receiving kidney transplants. A dose of 1 mg/kg is sufficient to completely block all the IL-2 receptors. It is administered in five doses at a 2-week interval where its elimination half-life is about 20 days. A combination of several other immunosuppressive agents including cyclosporine (or tacrolimus, rapamycin), mycophenolate mofetil and corticosteroids can be used with daclizumab. When it is used in combination with tacrolimus, the doses of tacrolimus are reduced. After tissue transplantation, the addition of daclizumab to the standard immunosuppressive regimen produces reduction in tissue rejection up to 50%. Daclizumab can cause hypersensitivity reactions, but it does not cause cytokine-release syndrome. There is a low incidence of... 

Basiliximab is used for the prophylaxis of acute rejection for patients undergoing kidney transplantation where it is employed in combination with other standard immunosuppressive therapy regimens. After tissue transplantation, its addition to the standard immunosuppressive regimen results in inhibiting tissue rejection up to approximately 30%. Both daclizumab and basiliximab have similar effects on the expression of IL-2a and -(3 chains. 

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