TY - JOUR
T1 - Gene therapy to improve pancreatic islet transplantation for Type 1 diabetes mellitus
AU - Hughes, Amy
AU - Jessup, Claire
AU - Drogemuller, Chris
AU - Mohanasundaram, Daisy
AU - Milner, Clyde
AU - Rojas-Canales, D
AU - Russ, Graeme
AU - Coates, P
PY - 2010
Y1 - 2010
N2 - Pancreatic islet transplantation is a promising treatment option for Type 1 Diabetics, offering improved glycaemic control through restoration of insulin production and freedom from life-threatening hypoglycaemic episodes. Implementation of the Edmonton protocol in 2000, a glucocorticoid-free immunosuppressive regimen has led to improved islet transplantation success. >50% of islets are lost post-transplantation primarily through cytokine-mediated apoptosis, ischemia and hypoxia. Gene therapy presents a novel strategy to modify islets for improved survival post-transplantation. Current islet gene therapy approaches aim to improve islet function, block apoptosis and inhibit rejection. Gene transfer vectors include adenoviral, adeno-associated virus, herpes simplex virus vectors, retroviral vectors (including lentiviral vectors) and non-viral vectors. Adeno-associated virus is currently the best islet gene therapy vector, due to the vectors minimal immunogenicity and high safety profile. In animal models, using viral vectors to deliver genes conferring local immunoregulation, anti-apoptotic genes or angiogenic genes to islets can significantly improve islet survival in the early post-transplant period and influence long term engraftment. With recent improvements in gene delivery and increased understanding of the mechanisms underlying graft failure, gene therapy for islet transplantation has the potential to move closer to the clinic as a treatment for patients with Type 1 Diabetes.
AB - Pancreatic islet transplantation is a promising treatment option for Type 1 Diabetics, offering improved glycaemic control through restoration of insulin production and freedom from life-threatening hypoglycaemic episodes. Implementation of the Edmonton protocol in 2000, a glucocorticoid-free immunosuppressive regimen has led to improved islet transplantation success. >50% of islets are lost post-transplantation primarily through cytokine-mediated apoptosis, ischemia and hypoxia. Gene therapy presents a novel strategy to modify islets for improved survival post-transplantation. Current islet gene therapy approaches aim to improve islet function, block apoptosis and inhibit rejection. Gene transfer vectors include adenoviral, adeno-associated virus, herpes simplex virus vectors, retroviral vectors (including lentiviral vectors) and non-viral vectors. Adeno-associated virus is currently the best islet gene therapy vector, due to the vectors minimal immunogenicity and high safety profile. In animal models, using viral vectors to deliver genes conferring local immunoregulation, anti-apoptotic genes or angiogenic genes to islets can significantly improve islet survival in the early post-transplant period and influence long term engraftment. With recent improvements in gene delivery and increased understanding of the mechanisms underlying graft failure, gene therapy for islet transplantation has the potential to move closer to the clinic as a treatment for patients with Type 1 Diabetes.
KW - Angiogenic
KW - Anti-apoptotic
KW - Gene therapy
KW - Immunomodulatory
KW - Islet transplantation
KW - Type 1 diabetes
KW - Viral vectors
UR - http://www.scopus.com/inward/record.url?scp=79952115861&partnerID=8YFLogxK
U2 - 10.2174/157339910793360897
DO - 10.2174/157339910793360897
M3 - Article
SN - 1573-3998
VL - 6
SP - 274
EP - 284
JO - Current Diabetes Reviews
JF - Current Diabetes Reviews
IS - 5
ER -