Cytoprotection of beta cells: rational gene transfer strategies.
Gene transfer to pancreatic islets may prove useful in preventing islet cell destruction and prolonging islet graft survival after transplantation in patients with type 1 diabetes mellitus (T1DM). Potentially, a host of therapeutically relevant transgenes may be incorporated into an appropriate gene delivery vehicle and used for islet modification. An increasing understanding of the molecular pathogenesis of immune-mediated beta cell death has served to highlight molecules which have become suitable candidates for promoting islet cell survival in the face of oxidative stress. This review aims to give an overview of some conventional gene transfer strategies aimed at promoting islet cell survival in the face of cytokine onslaught. These strategies target three aspects of islet cell physiology: redox status and antioxidant defence, anti-apoptotic gene expression and mediators of cytokine signal transduction pathways.
McCabe
Cillian
C
Regenerative Medicine Institute, National Centre for Biomedical Engineering Sciences, National University of Ireland Galway, Galway, Ireland.
Samali
Afshin
A
O'Brien
Timothy
T
D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000473:pathology / Q000601:surgery*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007515:Islets of Langerhans / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000473:pathology; D014184:Transplantation, Homologous; D014944:World Health Organization