Gene Combination Transfer to Block Autoimmune Damage in Transplanted Islets of Langerhans |
| |
| Authors: | Suzanne Bertera Angela M. Alexander Megan L. Crawford Glenn Papworth Simon C. Watkins Paul D. Robbins Massimo Trucco |
| |
| Affiliation: | 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, |
| |
| Abstract: | Islet transplantation therapy would be applicable to awider range of diabetic patients if donor islet acceptanceand protection were possible without systemic immunosuppressionof the recipient. To this aim, gene transferto isolated donor islets ex vivo is one method that hasshown promise. This study examines the combined effect ofselected immunomodulatory and anti-inflammatory genesknown to extend the functional viability of pancreatic isletgrafts in an autoimmune system. These genes, indoleamine2,3-dioxygenase (IDO), manganese superoxide dismutase(MnSOD), and interleukin (IL)-1 receptor antagonist protein(IRAP), were transferred to isolated NOD donor isletsex vivo then transplanted to NODscid recipients and evaluatedin vivo after diabetogenic T-cell challenge. The lengthof time the recipient remained euglycemic was used to measurethe ability of the transgenes to protect the graft fromautoimmune destruction. Although the results of these cotransfectionsgave little evidence of a synergistic relationship,they were useful to show that gene combinations can be used to more efficiently protect islet grafts from diabetogenicT cells. |
| |
| Keywords: | |
|
|
