- 作者: Hua Li; Xinyan Li; Karen S. L. Lam; Sidney Tam; Weidong Xiao; Ruian Xu
- 作者服務機構: Gene Therapy Laboratory, Genome Research Centre,The University of Hong Kong, Hongkong, P.R. China; Pharmacology Department, Pharmaceutical College,Dalian Medical University, Dalian, Liaoning, P.R. China; Pharmaceutical College, Shanghai JiaoTong University,Shanghai, P.R. China
- 中文摘要: --
- 英文摘要: Inducing autologous liver cells to differentiate into endocrine b 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 insulinproducing cells and to explore the origin of these cells. Here we used 4 9 10e11 AAV to deliver pdx-1 to STZinduced 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 realtime 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.
- 中文關鍵字: --
- 英文關鍵字: Oval stem cells; pdx-1; Adeno-associated virus; Differentiation; Insulin