Adeno-associated virus-mediated pancreatic and duodenal homeobox gene-1 expression enhanced differentiation of hepatic oval stem cells to insulin-producing cells in diabetic rats

J Biomed Sci. 2008 Jul;15(4):487-97. doi: 10.1007/s11373-008-9233-3. Epub 2008 Feb 6.


Inducing autologous liver cells to differentiate into endocrine beta cell has been a potential strategy for the treatment of type 1diabetes. However it is still not known which sub-population cells in the liver was responsible for this developmental shift. Pancreatic and duodenal homeobox gene 1 (pdx-1), a crucial transcription factor in pancreatic islet development and differentiation, has attracted much interests in beta cell differentiation experiments. This study was conducted to evaluate whether pdx-1 gene delivered by adeno-associated virus (AAV) could induce autologous liver cells to differentiate into insulin-producing cells and to explore the origin of these cells. Here we used 4 x 10e(11) AAV to deliver pdx-1 to STZ-induced diabetic rats via the portal vein. Immunofluorescent staining showed more insulin-positive cells, which had similar morphology with hepatic oval stem cells and were positive for hepatic oval stem cell markers, Thy-1 and cytokeratin 19 (ck19). In addition to the expression of pdx-1, insulin1 and insulin2, RT-PCR and quantitative real-time PCR also detected significantly higher levels of other important transcription factors in AAV-pdx-1 treated diabetic rat livers. AAV-pdx-1 treated diabetic rats showed partially ameliorated hyperglycemia, better gain of body weight and improved lipid levels. Our data indicated that rat hepatic oval stem cells were differentiated into bioactive insulin-producing cells by AAV-pdx-1 delivery in diabetic rats, with promoted expression of some transcription factors necessary for beta cell development and function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Body Weight
  • Cell Differentiation*
  • Dependovirus / genetics
  • Diabetes Mellitus, Experimental / therapy*
  • Duodenum / metabolism*
  • Genes, Homeobox / genetics*
  • Genetic Therapy*
  • Genetic Vectors
  • Hepatocytes / cytology
  • Hyperglycemia
  • Insulin-Secreting Cells / cytology*
  • Lipid Metabolism
  • Male
  • Pancreas / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells / cytology*
  • Transcription Factors / genetics
  • Treatment Outcome


  • Biomarkers
  • Transcription Factors