Conversion of Immortal Liver Progenitor Cells Into Pancreatic Endocrine Progenitor Cells by Persistent Expression of Pdx-1
Conversion of Immortal Liver Progenitor Cells Into Pancreatic Endocrine Progenitor Cells by Persistent Expression of Pdx-1
复制标题
通过持续表达 Pdx-1 将永生肝祖细胞转化为胰腺内分泌祖细胞
DOI：
10.1002/jcb.21617
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发表时间：
2008-05-01
影响因子：
4
通讯作者：
Hu, Yi-Ping
中科院分区：
文献类型：
--
作者：
Jin, Cai-Xia;Li, Wen-Lin;Hu, Yi-Ping
The conversion of explandable 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 rice to insulin-producing cells directly. EGFP/Pdx-1 LEPCs proliferated vigorously and Pax4, Pax6, IsI1, 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. (C) 2007 Wiley-Liss, Inc.
