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BACKGROUND This report describes the preclinical pharmacological profile of the new rapamycin analog, SDZ RAD, i.e., 40-O-(2-hydroxyethyl)-rapamycin. METHODS The pharmacological effects of SDZ RAD were assessed in a variety of in vitro and in vivo models, which included an autoimmune disease model as well as kidney and heart allotransplantation models(More)
Hearts from alpha1,3-galactosyltransferase knockout pigs (GalT-KO, n = 8) were transplanted heterotopically into baboons using an anti-CD154 monoclonal antibody-based regimen. The elimination of the galactose-alpha1,3-galactose epitope prevented hyperacute rejection and extended survival of pig hearts in baboons for 2-6 months (median, 78 d); the(More)
Cell-based diabetes therapy requires an abundant cell source. Here, we report reversal of diabetes for more than 100 d in cynomolgus macaques after intraportal transplantation of cultured islets from genetically unmodified pigs without Gal-specific antibody manipulation. Immunotherapy with CD25-specific and CD154-specific monoclonal antibodies, FTY720 (or(More)
The replication of porcine endogenous retrovirus subgroup A (PERV-A) and PERV-B in certain human cell lines indicates that PERV may pose an infectious risk in clinical xenotransplantation. We have previously reported that human-tropic PERVs isolated from infected human cells following cocultivation with miniature swine peripheral blood mononuclear cells(More)
Xenotransplantation using porcine cells, tissues, or organs may offer a potential solution for the shortage of allogeneic human organs. Prior to the clinical use of porcine xenotransplants, three main hurdles must be overcome: immunologic rejection, physiologic incompatibility, and risk of transmission of porcine pathogens. Designated pathogen-free breeding(More)
Heterotopic cardiac xenotransplantation from alpha1,3-galactosyltransferase gene-knockout (GalT-KO) swine to baboons was performed to characterize immunological reaction to the xenograft in the absence of anti-Gal antibody-mediated rejection. Eight baboons received heterotopic cardiac xenografts from GalT-KO porcine donors. All baboons were treated with(More)
The histology of epithelium-free areas in the subcapsular region of the thymus was studied in Wistar rats. Lymphocytes in these areas were CD4/CD8 double-positive, TCR alpha/beta positive in low intensity, and in CD5 labeling either negative or positive in low intensity. There was a high proliferative activity as assessed by bromodeoxyuridine incorporation(More)
We studied the effect of Cyclosporin A on the thymus in rats. A daily subcutaneous injection of Cyclosporin A at a dose of 45 mg/kg body weight in young adult rats resulted in a 100% mortality within two weeks. Daily administration of 15 mg/kg for two weeks was well tolerated. Rats treated at this dose showed whole blood Cyclosporin concentrations around 6(More)
The thymus of diabetes prone BB rats (DP) was studied and compared with diabetes resistant (DR) BB rats and normal WAG rats. Thymuses were obtained from 4-5 week old animals, i.e. before the onset of disease. Analysis included specific immune histology using a panel of monoclonal antibodies directed against markers both on thymocytes and stromal cells. No(More)
BACKGROUND In vivo xenotransplantation modeling in large animal species is often performed in nonhuman primates, including baboons. For proper data interpretation, reference values for clinical chemistry and hematology are required. METHODS These values are available from baseline levels in animals subjected to tolerability/pharmacokinetic studies. For(More)