Adeno-associated virus transduction of islets with interleukin-4 results in impaired metabolic function in syngeneic marginal islet mass transplantation.
Previous studies suggest that therapeutic expression of interleukin (IL)-4 by islet cells improves their efficacy in transplantation models directed at reversing type 1 diabetes. We investigated the effects of introducing IL-4 into islets with recombinant adeno-associated virus (rAAV) on the reversal of hyperglycemia in a syngeneic marginal islet mass transplantation model. C57BL/6 islets were mock-transduced or transduced with rAAV expressing murine IL-4 (rAAV-IL-4) or rAAV expressing green fluorescent protein (rAAV-GFP) before transplantation of a marginal mass into diabetic mice. Normoglycemia was achieved in only 1/7 mice receiving rAAV-IL-4 transduced islets in comparison to 6/6 mock-transduced and 4/6 rAAV-GFP transduced animals. The failure of IL-4 expressing islets was not associated with cellular toxicity of rAAV or impairment of glucose-stimulated insulin release in vitro. Islet expression of IL-4 led to impaired metabolic function in mice receiving a marginal mass of syngeneic islets.
Zhang
Y Clare
YC
Department of Pathology, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA.
Molano
R Damaris
RD
Pileggi
Antonello
A
Powers
Matthew
M
Cross
Jeffrey
J
Wasserfall
Clive
C
Scott-Jorgensen
Marda
M
Campbell-Thompson
Martha
M
Crawford
James M
JM
Flotte
Terence
T
Ellis
Tamir M
TM
Ricordi
Camillo
C
Atkinson
Mark A
MA
Inverardi
Luca
L
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001786:Blood Glucose; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D005822:Genetic Vectors; D006085:Graft Survival; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D015847:Interleukin-4 / Q000235:genetics*; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D014161:Transduction, Genetic; D014185:Transplantation, Isogeneic
D001786:Blood Glucose; D007328:Insulin; D015847:Interleukin-4