No abstract

Abstract. The biohazards caused by the viral delivery of pancreatic duodenal homeobox gene 1 (Pdx1) to the murine liver limits its application. We aimed to evaluate the feasibility of hydrodynamics-based transfection (HBT) with Pdx1 in improving hyperglycemia. Murine hepatocellular carcinoma (Hepa1-6) cells were transfected with the Pdx1-expressing plasmid, pcdna3.1/V5-His a (pcdna)-Pdx1. Hepatic delivery of pcdna-Pdx1 or pcdna in streptozocin-induced diabetic mice was achieved by HBT. The sequential serum glucose and alanine aminotransferase (aLT) levels were assessed. On the 3 rd day after transfection, the transfection efficiency in the Hepa1-6 cells and the mice livers was 5% and 0.35 %, respectively. At 1 wk after HBT, asides from hepatic expression of insulin, the diabetic mice transfected with pcDNA-Pdx1 had a significantly lower sugar (211 ± 61.6 vs. 413 ± 62 mg/dL; p = 0.002) level than those transfected with pcDNA; however, the difference diminished afterward. No significant difference in the ALT levels was observed between the 2 groups. no mortality was noted in the mice transfected with pcdna-Pdx1. The hypoglycemic effect of Pdx1 delivered by HBT was transient and associated with negligible complications. in studies on the short-term biological effects of Pdx1 in vivo, HBT is a potential alternative to viral delivery of Pdx1 to the murine liver.