![]() Rejection of human islets and human HLA-A2.1 transgenic mouse islets by alloreactive human lymphocytes in immunodeficient NOD-scid and NOD-Rag1(null)Prf1(null) mice. 2008 13(6):633–638.īanuelos SJ, Shultz LD, Greiner DL, Burzenski LM, Gott B, Lyons BL, Rossini AA, Appel MC. Causes of limited survival of microencapsulated pancreatic islet grafts. We have produced a SCID hairless outbred mouse, SHOTM-PrkdcscidHrhr (SHOTM), by crossing a SCID mouse, Crl:HA-Prkdcscid (outbred SCID) with an immunocompetent outbred hairless mouse, Crl:SKH1-Hrhr (SKH1). Safety and viability of microencapsulated human islets transplanted into diabetic humans. Tuch BE, Keogh GW, Williams LJ, Wu W, Foster JL, Vaithilingam V, Philips R. We were interested in evaluating SCID mice in both hFcRn Tg and C57BL/6 varieties with three different antibodies, Humira®, mAbX and mAbX-YTE. Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes: first two cases. As another result, the maintained viability of transplanted islets on the NOD/SCID background emphasized a critical role of protective mechanisms in autoimmune diabetes transplanted subjects due to specific immunoregulatory effects provided by IL-4 and IL-10.Ĭalafiore R, Basta G, Luca G, Lemmi A, Montanucci MP, Calabrese G, Racanicchi L, Mancuso F, Brunetti P. In conclusion, this study showed that the hu-NOD/SCID mouse is not a suitable preclinical model to study the allograft rejection mechanisms of encapsulated human islets. Mouse mutants with deleted, defective, or misexpressed genes that encode activities necessary for glycosylation have led the way to identifying key functions of glycans in biology. The ability of encapsulated islets to survive in this mouse model might partly be attributed to the presence of Th2 cytokines IL-4 and IL-10, which are known to induce graft tolerance. Though the engrafted T cells caused a small fibrotic overgrowth around the microencapsulated human islets, this failed to stop the encapsulated islets from functioning in the diabetic recipient mice. In this model, human T cell engraftment could be achieved, and CD45+ cells were observed in the spleen and peripheral blood. In this study, we investigated the usefulness of NOD/SCID mice reconstituted with human PBMCs (called humanized NOD/SCID mice) as a preclinical model. This warrants the need for a suitable small animal model. The major reason for this is limited understanding of what occurs when encapsulated human islets are allografted. This enzyme recognizes and is activated by DNA strand breaks. Recent clinical trials using microencapsulated human islets in barium alginate showed the presence of dense fibrotic overgrowth around the microcapsules with no viable islets. Poly (ADP-ribose) polymerase (113 kDa PARP-1) is a constitutive factor of the DNA damage surveillance network developed by the eukaryotic cell to cope with the numerous environmental and endogenous genotoxic agents. Despite encouraging results in animal models, the transplantation of microencapsulated islets into humans has not yet reached the therapeutic level.
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