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β-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas

Gene Therapy volume 10, pages 15–23 (2003)Cite this article

Abstract

β-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 β-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, β-cell neogenesis induced by adenovirus-mediated expression of pdx-1 provides a novel strategy for gene therapy for a cure for diabetes mellitus.

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Acknowledgements

We are grateful to Mr T. Mitsu (Oriental Yeast Co., Japan) and Ms M. Yamamoto (Osaka University, Japan) for technical assistance and to Dr Y. Kajimoto (Osaka University, Japan) for rabbit anti-mouse pdx-1 serum. This work was supported by a grant from the Research for the Future Program (JSPS-RFTF97I00201) of the Japan Society for the Promotion of Science (JSPS). This work was also supported by a grant from the Japanese Ministry of Education, Science, Sports and Culture.

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Authors and Affiliations

  1. Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan

    H Taniguchi, E Yamato, F Tashiro & J Miyazaki

  2. Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

    H Taniguchi, H Ikegami & T Ogihara

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  1. H Taniguchi
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Taniguchi, H., Yamato, E., Tashiro, F. et al. β-cell neogenesis induced by adenovirus-mediated gene delivery of transcription factor pdx-1 into mouse pancreas. Gene Ther 10, 15–23 (2003). https://doi.org/10.1038/sj.gt.3301846

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