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

Gene Ther. 2003 Jan;10(1):15-23. doi: 10.1038/sj.gt.3301846.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Division
  • Common Bile Duct / metabolism
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / therapy*
  • Gene Expression
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage
  • Homeodomain Proteins*
  • Immunohistochemistry
  • Injections
  • Islets of Langerhans / cytology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / genetics*
  • Trans-Activators / genetics*
  • Transduction, Genetic / methods

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Neurog3 protein, mouse
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein