No description available.

No description available.

Background: Organs transplanted between discordant species such as pig-to-primate, undergo hyperacute rejection due to the presence of natural xenogenic antibodies. Hyperacute rejection xenograft rejection can now be controlled by various approaches, but other immunological barriers have yet to be overcome. Polyspecific HLA antibodies often crossreact with other HLA antigens through so called public and private determinants. Swine leucocyte antigens share approximately 75-87% homology with HLA and as such, it may be expected that some HLA antibodies would react with certain SLA antigens. In an attempt to evaluate this possible occurrence, sera were selected from individuals with varying panel reactive antibodies. Methods: Naturally occurring anti-pig antibodies were absorbed using an excess of leucocyte depleted washed pig red blood cells (PRBC). Anti-HLA/SLA cross reactivity was investigated by 1) testing the pre and post-absorbed sera against a panel of out bred pig splenocytes; 2) HLA class I and II antibodies were absorbed out using pooled EBV cell and human platelets; 3) Human non-Gala1,3Gal antibody was adsorbed onto, then eluted from pig splenocytes. The presence of HLA specific antibody in the eluates was investigated. Results. Natural anti-pig antibody adsorption was confirmed in all sera by flow cytometry against PRBC. Anti-HLA activity was still present and undiminished post-PRBC-adsorption. Some HLA specific sera still reacted against some pigs after removal of natural antibody and no reactivity was identical to any other. Upon absorption of the HLA antibodies, the majority of anti-pig reactivity was abrogated. The eluates showed that HLA class I and II antibodies were eluted from pig splenocytes. In addition, the presence of a non-HLA antibody was also found. Conclusions: The results show that there is cross reactivity between IgG anti-HLA and pig lymphocytes.

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No description available.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 5 uppsatser.

Det råder organbrist och en alternativ lösning är xenotransplantation. Tekniken är idag klinisk verklighet inom hjärtklaffskirurgin och diabetesvården. Sjuksköterskan möter således xenotransplanterade patienter och patienter som väntar på transplantation. Det är betydelsefullt att sjuksköterskan tillgodoser varje individs unika omvårdnadsbehov. Individen behöver både ta ställning till att ta emot organ och donera. Syftet med litteraturstudien var att beskriva patienters attityder till xenotransplantation. Till resultatet användes 14 kvalitativa och kvantitativa artiklar som granskades och analyserades. Det framkom fem kategorier: oro för personlighetspåverkan, rädsla för avstötning och smittspridning, individuella påverkansfaktorer, transplantatets ursprung och överlevnadsinstinktens påverkan samt informationens effekt. Resultatet visade att patienter var mer intresserade av transplantatets funktion än dess ursprung. Det fanns patienter som uttryckte oro för personlighetsförändring. Oron kan förklaras av att xenotransplantation är en relativt ny teknik. Män hade en mer positiv attityd än kvinnor till xenotransplantation. Vidare framkom det att transplantation med organ uppfattades som ett större intrång i kroppen, medan celler uppfattades som mer diffust. Genom att sjuksköterskan får ökad kunskap om patienters attityder till xenotransplantation kartläggs mer av patientens livsvärld, vilket skapar bättre förutsättningar för en god omvårdnad. Kommande forskning bör inriktas på patienter som genomgått xenotransplantation. / Organ shortage is a problem and an alternative solution is xenotransplantation. Xenotransplantation is currently clinical reality in heart valve surgery and diabetes care. The nurse meets xenotransplant patients and patients waiting for transplantation. It is important that the nurse meets each individual unique nursing care. Individuals need to make a commitment to both receiving and donation organs. The aim of this literature study was to describe patients attitudes toward xenotransplantation. The result was based on 14 qualitative and quantitative articles. The articles were reviewed and analyzed. It emerged five categories: concerns about the impact of personality, fear of rejection and infection, individual influences, graft origin and survival instincts impact and information effect. The result showed that patients were more interested in graft function than its origin. Anxiety can be explained by the fact that xenotransplantation is a relatively new technology. It was also found that an organ was perceived as a major intrusion into the body, while the cells were more diffuse. The conclusion is that the nurse may increase the knowledge of patients’ attitudes to xenotransplantation showed more of the patients life-world, creating better condition for good care. Future research should focus on already xenotransplant patients.

Indiana University-Purdue University Indianapolis (IUPUI) / Solid organ transplantation is severely limited by a shortage of available donor allografts. Pig-to-human xenotransplantation offers a potential solution to this growing problem. For xenotransplantation to achieve clinical relevance, both immunologic and physiologic barriers must be understood. Genetic modification of pigs has proven to be a valuable means of both studying and eliminating these barriers. The present body of work describes a method for greatly increasing the efficiency and precision of genome editing within the porcine genome. By combining non-integrating selection and homologous recombination of exogenous oligonucleotides, a method for rapidly creating genetic modification without reliance on phenotypic sorting was achieved. Furthermore this work employs the technique of CRISPR/Cas9-directed mutagenesis to create and analyze several new animal models of porcine-to-human xenotransplantation with respect to both immunologic and physiologic parameters. First, Isoglobotrihexosylceramide -a controversial glycan to the field of xenotransplantation- was studied in a knockout model and found not to affect human-anti-porcine humoral reactions. Second, a new combination of glycan modifications is described that significantly lowers the human anti-porcine humoral immune response. This model animal suggests that glycan-deletion alone will be sufficient to promote clinical application, and that conventional immunosuppression will be successful in mediating the human cellular response. Finally, two potential physiologic barriers to xenotransplantation are studied in genetically modified model animals. Xenogenic consumption of human platelets was studied across hepatic and renal organ systems; xenogenic platelet consumption was reduced by glycan modifications to the porcine liver while human platelet sequestration was not identified in the study of renal endothelium. Porcine FcRN –an essential receptor expressed in kidneys to maintain serum proteostasis- was studied as a final potential barrier to pig-to human renal transplantation. Because albumin is the primary driver of serum oncotic pressure, the protein-protein interaction of endogenous porcine FcRN and human albumin was studied. Porcine FcRN was found capable of binding human albumin under physiologic parameters. In summary, the results of the present work suggest that the salient barriers to clinical xenotransplantation have been removed and that porcine-to human renal transplantation may soon offer an answer to the current organ shortage.

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