Transplantation of islets transduced with CTLA4-Ig and TGFbeta using adenovirus and lentivirus vectors

Transplant Immunology
Justin R FernandesGordon C Weir

Abstract

A major problem facing islet transplantation is immune destruction of grafts by transplant rejection and autoimmunity. Some success in prolonging graft rejection has been obtained by transducing islets prior to transplantation with adenoviral (Ad) vectors containing CTLA4-Ig and TGFbeta. The purpose of this study was to see if lentiviral (LV) vectors would provide superior results compared with adenoviral vectors. Islets were isolated from Sprague-Dawley rats and transduced with Ad or LV vectors containing LacZ, CTLA4-Ig, CTLA4, and TGFbeta1 using various MOIs. Islets transduced with LV were healthy as judged by DNA and insulin content, and insulin secretion. Using the kidney capsule transplant site, 500 transduced rat islets were transplanted into streptozotocin diabetic B6AF1 mice. Maintenance of normoglycemia was prolonged in recipient mice carrying islets transduced with Ad vectors containing CTLA4-Ig, CTLA4, and TGFbeta1. Return of hyperglycemia in controls was 17-18 days while loss of function for the experimental groups occurred at 20-27 days. For the lentivirus transduced islets, rejection of controls was 20+/-1.6 days, for CTLA4-Ig was 42+/-21 days and for TGFbeta was 28+/-3.2 days. Although islets transduced with eith...Continue Reading

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Citations

May 20, 2009·Virology Journal·Anthony T CraigRoland A Owens
Jun 13, 2012·International Journal of Endocrinology·Feng-Cheng ChouHuey-Kang Sytwu
Apr 21, 2010·Immunology and Cell Biology·Francesco L IerinoMauro S Sandrin
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