Gene Combination Transfer to Block Autoimmune Damage in Transplanted Islets of Langerhans |
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| Authors: | Suzanne Bertera Angela M Alexander Megan L Crawford Glenn Papworth Simon C Watkins Paul D Robbins Massimo Trucco |
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| Institution: | 1. Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh School of Medicine, Rangos Research Center, Children''s Hospital of Pittsburgh, 3460 Fifth Avenue, Pittsburgh, Pennsylvania, 15213, USA.;2. Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.;3. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA, |
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| Abstract: | Islet transplantation therapy would be applicable to a
wider range of diabetic patients if donor islet acceptance
and protection were possible without systemic immunosuppression
of the recipient. To this aim, gene transfer
to isolated donor islets ex vivo is one method that has
shown promise. This study examines the combined effect of
selected immunomodulatory and anti-inflammatory genes
known to extend the functional viability of pancreatic islet
grafts in an autoimmune system. These genes, indoleamine
2,3-dioxygenase (IDO), manganese superoxide dismutase
(MnSOD), and interleukin (IL)-1 receptor antagonist protein
(IRAP), were transferred to isolated NOD donor islets
ex vivo then transplanted to NODscid recipients and evaluated
in vivo after diabetogenic T-cell challenge. The length
of time the recipient remained euglycemic was used to measure
the ability of the transgenes to protect the graft from
autoimmune destruction. Although the results of these cotransfections
gave little evidence of a synergistic relationship,
they were useful to show that gene combinations can be used to more efficiently protect islet grafts from diabetogenic
T cells. |
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