In addition, the effect of microwave sterilization on tissue integrity was examined. Optimized microwave parameters were used to determine whether inactivation of pathogenic bacteria from bovine pericardium could be achieved. Two common pathogenic species of bacteria, Escherichia coli and Staphylococcus aureus, were used as test microorganisms. This study examined a novel technique using nonthermal microwave radiation that could lead to the inactivation of bacteria in bovine pericardial biomaterial without compromising valve durability. Therefore, improved techniques are needed that are cost effective and do not disrupt the physical properties, functionality, and lifespan of the valvular leaflets. These techniques, however, can be problematic because they can be expensive and lead to a reduction in tissue integrity. Methods currently available for sterilization of biomaterial for transplantation include the application of gamma radiation and chemical sterilants. Model-related morbidity due to variety of causes was seen in these experiments, suggesting that further therapeutic interventions, including candidate genetic modifications of donor pigs, may be necessary to reduce late morbidity in this model to a clinically manageable level.īioprosthetic valves created from chemically treated natural tissues such as bovine pericardial biomaterial are used as heart valve scaffolds. This result identifies a critical role for B cells in the mechanisms of elicited anti-non-Gal antibody and delayed xenograft rejection. B-cell depletion persisted for over 2 months, and elicited anti-non-Gal antibody production remained suppressed for the duration of graft follow-up. Peritransplant B-cell depletion using 4 weekly doses of anti-CD20 antibody in the context of an established ATG, anti-CD154 and MMF-based immunosuppressive regimen prolonged GTKO.hCD46Tg graft survival for up to 236 days (n = 9, median survival 71 days and mean survival 94 days). We report significant prolongation of heterotopic alpha Galactosyl transferase "knock-out" and human CD46 transgenic (GTKO.hCD46Tg) pig cardiac xenografts survival in specific pathogen free baboons. Rejection in Gal knockout (GTKO) pigs due to elicited non-Gal antibody response required further genetic modifications of donor pigs and better control of the B-cell response to xenoantigens. Xenotransplantation of genetically modified pig organs offers great potential to address the shortage of human organs for allotransplantation. Strategies have been developed to prevent PERV transmission, including selection of PERV-C-negative, low-producer pigs, generation of an effective vaccine, selection of effective antiretrovirals, and generation of animals transgenic for a PERV-specific short hairpin RNA inhibiting PERV expression by RNA interference. Highly sensitive and specific methods have been developed to analyze the PERV status of donor pigs and to monitor recipients for PERV infection. To date, all experimental, preclinical, and clinical xenotransplantations using pig cells, tissues, and organs have not shown transmission of PERV. Like all retroviruses, they may induce tumors and/or immunodeficiencies. PERVs may adapt to host cells by varying the number of LTR-binding transcription factor binding sites. Infection of ecotropic PERV-C is limited to pig cells. Human-tropic PERV-A and -B are present in all pigs and are able to infect human cells. Whereas most microorganisms may be eliminated by pathogen-free breeding of the donor animals, porcine endogenous retroviruses (PERVs) cannot be eliminated, since these are integrated into the genomes of all pigs. Xenotransplantation may be a solution to overcome the shortage of organs for the treatment of patients with organ failure, but it may be associated with the transmission of porcine microorganisms and the development of xenozoonoses.
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