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
References
Aug 7, 1992·Science·D J LenschowJ A Bluestone
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J C CarelP E Lacy
May 15, 1995·Transplantation·A A ChahineH T Lau
Apr 12, 1996·Science·L NaldiniD Trono
Jun 1, 1996·The Journal of Experimental Medicine·T L WalunasJ A Bluestone
Aug 15, 1997·The Journal of Clinical Investigation·P J SimeJ Gauldie
Mar 6, 1998·The Journal of Endocrinology·J G MableyI C Green
Apr 9, 1998·Transplantation Proceedings·A L GainerJ F Elliott
Jun 10, 1998·Immunity·C KingN Sarvetnick
Mar 20, 1999·Transplantation Proceedings·C LiuK L Brayman
Jul 13, 1999·Transplantation·S FengG C Weir
Sep 8, 1999·The Journal of Experimental Medicine·T T ChangA H Sharpe
Oct 27, 1999·Diabetes·N GiannoukakisM Trucco
Apr 29, 2000·Cell·V ZennouP Charneau
Sep 26, 2000·Molecular and Cellular Biology·S R CherryR Jaenisch
Jun 28, 2002·Diabetes·Edmond A RyanA M James Shapiro
Jul 11, 2002·Diabetologia·F KimuraM Miyasaka
Feb 28, 2003·Transplantation·Wai Keong WongJohn A Kirby
Mar 29, 2003·Expert Opinion on Biological Therapy·Nader Najafian, Samia J Khoury
Jun 6, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiaobing YuLinzhao Cheng
Citations
May 20, 2009·Virology Journal·Anthony T CraigRoland A Owens
Aug 13, 2009·Journal of Biomedical Science·Feng-Cheng Chou, Huey-Kang Sytwu
Apr 21, 2010·Diabetologia·M ShimodaP A Grayburn
Jun 13, 2012·International Journal of Endocrinology·Feng-Cheng ChouHuey-Kang Sytwu
Apr 21, 2010·Immunology and Cell Biology·Francesco L IerinoMauro S Sandrin
Aug 22, 2007·Cell Transplantation·H CallewaertC Mathieu
Nov 30, 2007·Gene Therapy·A Zaldumbide, R C Hoeben
Feb 6, 2008·Journal of Cellular Biochemistry·Ahter Dilsad SanliogluSalih Sanlioglu
Jun 8, 2006·Xenotransplantation·Zhong HeJan Holgersson
Dec 16, 2010·Human Vaccines·Mark C JohnsonRoland Tisch
Jul 14, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Reginald M GorczynskiIvo Boudakov