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  • 1
    ISSN: 1432-2277
    Keywords: Key words Xenotransplantation ; 15-deoxyspergualin ; Guinea pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study aimed to investigate the effects of 15-deoxyspergualin (DSG), tacrolimus (FK 506) and cyclosporin A (CyA), alone or in combination, on delayed xenograft rejection (DXR). We used the guinea-pig-to-C6-deficient (C6–)-PVG-rat heart transplantation model, since in this strain combination, hyperacute rejection is avoided. In C6- control rats, the guinea pig xenografts survived for 39.2 ± 6.3 h (mean ± SD). Splenectomy alone resulted in a xenograft survival of 71.8 ± 7.8 h, but the addition of CyA or FK 506 did not further improve graft survival (73.6 ± 3.0 h and 72.0 ± 17.6 h, respectively). In contrast, DSG treatment increased graft survival to a mean of 99.8 ± 9.2 h. When CyA or FK 506 was combined with DSG, no additional effects were observed (105 ± 24.3 h and 95.1 ± 5.6 h, respectively). DSG alone or in combination with FK 506 or CyA resulted in a significant reduction in the serum IgM levels and reduced the deposits of IgM and IgG in rejected grafts. However, all xenografts were still heavily infiltrated by ED1 + macrophages, regardless of the treatment used. Thus, DSG treatment resulted in moderate prolongation of xenograft survival in C6– rats. The effect seems to be related to suppression of xenoreactive antibody production. To prolong xenograft survival further, strategies that inhibit macrophage infiltration seem required.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1436-0691
    Keywords: Key words Clinical xenoislet transplantation ; Xenoanti-bodies ; Porcine endogenous retrovirus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 1990–1993, eight diabetic renal transplant patients had porcine fetal islets injected intraportally at Huddinge Hospital in Stockholm. Four of the patients had evidence of xenograft function reflected in the excretion of small amounts of porcine C-peptide. Two patients had the porcine fetal islets placed under the capsule of a simultaneously transplanted kidney. In one of these patients, a graft biopsy specimen taken 3 weeks after transplantation revealed morphologically intact epithelial cells staining positively for insulin and glucagon. The insulin production was in all instances insufficient to affect the patient's insulin requirements. All patients formed specific xenoantibodies (mostly anti-Gal); presumably, most of the xenoislets were destroyed by rejection. On follow-up studies carried out 6–8 years after xenotransplantation, most patients still had higher-than-pretransplant levels of xenoantibodies. There was no evidence of transmission of porcine endogeneous retroviruses to the patients. All patients expressed a positive attitude toward the use of animal tissue for treatment of disease, and none of the patients regretted participating in the trial. Cell transplantation is leading the way at present for clinical xenotransplantation. The finding that complement inhibition protects intraportally injected porcine islets from an injurious incompatibility reaction holds promise for future clinical application. A similar protective effect might be achievable with the use of islets from transgenic pigs expressing human complement receptors.
    Type of Medium: Electronic Resource
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