Conversion of immortal liver progenitor cells into pancreatic endocrine progenitor cells by persistent expression of Pdx-1
✍ Scribed by Cai-Xia Jin; Wen-Lin Li; Fang Xu; Zhen H. Geng; Zhi-Ying He; Juan Su; Xin-Rong Tao; Xiao-Yan Ding; Xin Wang; Yi-Ping Hu
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 425 KB
- Volume
- 104
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
The conversion of expandable liver progenitor cells into pancreatic beta cells would provide a renewable cell source for diabetes cell therapy. Previously, we reported the establishment of liver epithelial progenitor cells (LEPCs). In this work, LEPCs were modified into EGFP/Pdx‐1 LEPCs, cells with stable expression of both Pdx‐1 and EGFP. Unlike previous work, with persistent expression of Pdx‐1, EGFP/Pdx‐1 LEPCs acquired the phenotype of pancreatic endocrine progenitor cells rather than giving rise to insulin‐producing cells directly. EGFP/Pdx‐1 LEPCs proliferated vigorously and expressed the crucial transcription factors involved in beta cell development, including Ngn3, NeuroD, Nkx2.2, Nkx6.1, Pax4, Pax6, Isl1, MafA and endogenous Pdx‐1, but did not secrete insulin. When cultured in high glucose/low serum medium supplemented with cytokines, EGFP/Pdx‐1 LEPCs stopped proliferating and gave rise to functional beta cells without any evidence of exocrine or other islet cell lineage differentiation. When transplanted into diabetic SCID mice, EGFP/Pdx‐1 LEPCs ameliorated hyperglycemia by secreting insulin in a glucose regulated manner. Considering the limited availability of beta cells, we propose that our experiments will provide a framework for utilizing the immortal liver progenitor cells as a renewable cell source for the generation of functional pancreatic beta cells. J. Cell. Biochem. 104: 224–236, 2008. © 2007 Wiley‐Liss, Inc.