Cell based diabetes treatment in a preclinical model

Abstract

Cell-based approaches are emerging strategies for diabetes treatment. Our approach was to electroporate autologous primary hepatocytes with a plasmid construct encoding human proinsulin cDNA driven by a bifunctional promoter. Engineered hepatocytes were then transplanted into streptozotocin-induced diabetic cynomolgus macaques. In vitro studies confirmed the transfected hepatocytes had regulated insulin secretion in response to glucose and zinc. Diabetic monkeys transplanted with transfected hepatocytes had lower fasting blood glucose levels compared to controls and did not require exogenous insulin therapy to achieve this. Treated animals had post-transplant IVGTT curves for glucose similar to their pre-diabetic state but control animals had post-transplant IVGTT curves similar to their diabetic state. The area under the curve (AUC) for insulin was higher in the post-transplant state compared to the diabetic state in the treated monkeys. In controls, insulin AUC was lower post-transplant compared to the diabetic state.