Protection of Human Pancreatic Islets Using a Lentiviral Vector Expressing Two Genes: cFLIP and GFP

Cell Transplantation

Article

Elizabeth S. Fenjves¹  M. Sofia Ochoa¹  Armando Mendez¹  Carlota Gay-Rabinstein¹  Ingrid Pérez-Alvarez¹  Camillo Ricordi¹  Sirlene Cechin¹  Hirohito Ichii¹  Michael A. Curran² 

[1] Diabetes Research Institute, University of Miami School of Medicine, Miami, FL, USA;Memorial Sloan Kettering Cancer Center, New York, NY, USA;

关键词: Diabetes;    Pancreatic islet transplantation;    Feline immunodeficiency virus (FIV);    Gene therapy;    cFLIP;   

DOI  :  10.3727/096368908786516828

 received in 2007-05-27, accepted in 2008-01-30,  发布年份 2008

来源: Sage Journals

【 摘 要 】

Pancreatic islet transplantation can provide insulin independence to diabetic patients. However, apoptosis of islets often leads to early graft failure. Genetic engineering with protective gene(s) can improve the viability of these cells. Here we show successful transduction of human islets with a feline immunodeficiency virus (FIV) vector expressing both a cytoprotective (cFLIP) gene and the green fluorescent protein (GFP). Despite using low virus titers to maximize safety, transduced islets expressed both genes, resulting in improved β-cell metabolic activity and viability. Although only ~10% of total islet cells were transduced, the significant viability advantages suggest a “barrier” effect in which protecting the periphery of the islet shields the core. These results provide the first demonstration that a lentiviral vector can express two genes in islets. Furthermore, the engineered islets are resistant to a variety of apoptotic stimuli, suggesting the potential of this approach in enhancing the viability of transplanted cells.

【 授权许可】

Unknown   
© 2008 Cognizant Comm. Corp.