Research Article
Gene Therapy (2003) 10, 15–23. doi:10.1038/sj.gt.3301846
-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas
H Taniguchi1,2, E Yamato1, F Tashiro1, H Ikegami2, T Ogihara2 and J Miyazaki1
- 1Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan
- 2Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
Correspondence: J Miyazaki, Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Received 19 April 2002; Accepted 23 June 2002.
Abstract
-cell neogenesis is expected to provide a new therapy for diabetes. Numerous studies have demonstrated that transcriptional regulation involving pdx-1 is essential for endocrine neogenesis in vivo and in vitro. Therefore, it is possible that ectopic expression of pdx-1 in the pancreas could induce endocrine neogenesis. To test this possibility, we performed safe and efficient gene delivery of the pdx-1 gene into the mouse pancreas through the common bile duct using adenoviral vectors, and examined the effects of the ectopic expression of pdx-1. Here we show that adenovirus-mediated expression of pdx-1 can activate the endogenous pdx-1 gene, leading to
-cell neogenesis and ductal proliferation. This technique is similar to the endoscopic retrograde cholangiopancreatography, which has been already established as a safe procedure for humans. Thus,
-cell neogenesis induced by adenovirus-mediated expression of pdx-1 provides a novel strategy for gene therapy for a cure for diabetes mellitus.
Keywords:
-cell neogenesis, adenoviral vector, gene delivery, pdx-1, neurogenin3, ICBD injection
