Short Report

Pdx-1 or Pdx-1-VP16 protein transduction induces β-cell gene expression in liver-stem WB cells

Juliette Cuvelier Delisle^1,2,3 , Lionel Martignat^1,2,3 , Laurence Dubreil^4,5 , Pierre Saï^1,2,3 , Jean-Marie Bach^1,2,3 , Vanessa Louzier^1,2,3* and Steffi Bösch^1,2,3*

¹  UMR 707 IECM ENVN, F-44307 Nantes, France

²  UMR 707 IECM INRA, F-44307 Nantes, France

³  UMR 707 IECM Nantes University, F-44307 Nantes, France

⁴  UMR 703 ENVN, F-44307 Nantes, France

⁵  UMR 703 INRA, F-44307 Nantes, France

author email corresponding author email* Contributed equally

BMC Research Notes 2009, 2:3doi:10.1186/1756-0500-2-3

Published:	9 January 2009

Abstract

Background

Pancreatic duodenal homeobox-1 (Pdx-1) or Pdx-1-VP16 gene transfer has been shown to induce in vitro rat liver-stem WB cell conversion into pancreatic endocrine precursor cells. High glucose conditions were necessary for further differentiation into functional insulin-producing cells. Pdx-1 has the ability to permeate different cell types due to an inherent protein transduction domain (PTD). In this study, we evaluated liver-to-pancreas conversion of WB cells following Pdx-1 or Pdx-1-VP16 protein transduction.

Findings

WB cells were grown in high glucose medium containing Pdx-1 or Pdx-1-VP16 recombinant proteins for two weeks. β-like cell commitment was analysed by RT-PCR of pancreatic endocrine genes. We found that WB cells in high glucose culture spontaneously express pancreatic endocrine genes (Pdx-1, Ngn3, Nkx2.2, Kir6.2). Their further differentiation into β-like cells expressing genes related to endocrine pancreas development (Ngn3, NeuroD, Pax4, Nkx2.2, Nkx6.1, Pdx-1) and β-cell function (Glut-2, Kir6.2, insulin) was achieved only in the presence of Pdx-1(-VP16) protein.

Conclusion

These results demonstrate that Pdx-1(-VP16) protein transduction is instrumental for in vitro liver-to-pancreas conversion and is an alternative to gene therapy for β-cell engineering for diabetes cell therapy.