Transdifferentiation of hepatic oval cells into pancreatic islet beta-cells.

Insulin production by beta-cells derived from hepatic oval cells is a promising new approach for the treatment of diabetes. Hepatic oval cells can be redirected to the beta-cell linage by an appropriate combination of high extracellular glucose, specific extracellular matrix proteins (laminin and fibronectin), cytokines (activin A), and the expression of several differentiation-related transcription factors (Pdx-1, Ngn-3, MafA). We explore the process of hepatic oval cell transdifferentiation into pancreatic islet beta-cells and the cellular signaling pathways involved.

[1]  Philip N Benfey,et al.  Symmetry breaking in plants: molecular mechanisms regulating asymmetric cell divisions in Arabidopsis. , 2009, Cold Spring Harbor perspectives in biology.

[2]  S. Samson,et al.  Gene therapy with neurogenin 3 and betacellulin reverses major metabolic problems in insulin-deficient diabetic mice. , 2009, Endocrinology.

[3]  K. Zaret,et al.  Dynamic Signaling Network for the Specification of Embryonic Pancreas and Liver Progenitors , 2009, Science.

[4]  L. Martignat,et al.  Pdx-1 or Pdx-1-VP16 protein transduction induces β-cell gene expression in liver-stem WB cells , 2009, BMC Research Notes.

[5]  M. Grompe,et al.  Generation and Regeneration of Cells of the Liver and Pancreas , 2008, Science.

[6]  J. Brickman,et al.  Anterior definitive endoderm from ESCs reveals a role for FGF signaling. , 2008, Cell stem cell.

[7]  M. Ghoneim,et al.  Transplantation of insulin-producing clusters derived from adult bone marrow stem cells to treat diabetes in rats. , 2008, Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation.

[8]  I. Artner,et al.  MafA is a dedicated activator of the insulin gene in vivo. , 2008, The Journal of endocrinology.

[9]  James D. Johnson,et al.  Notch signalling suppresses apoptosis in adult human and mouse pancreatic islet cells , 2007, Diabetologia.

[10]  Philippe Morel,et al.  International trial of the Edmonton protocol for islet transplantation. , 2006, The New England journal of medicine.

[11]  S. Efrat,et al.  Differentiation of human liver-derived, insulin-producing cells toward the beta-cell phenotype. , 2005, Diabetes.

[12]  H. Kaneto,et al.  A Crucial Role of MafA as a Novel Therapeutic Target for Diabetes*♦ , 2005, Journal of Biological Chemistry.

[13]  B. Burkhardt,et al.  In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. , 2004, Diabetes.

[14]  T. Matsuoka,et al.  The MafA transcription factor appears to be responsible for tissue-specific expression of insulin. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Fujimiya,et al.  Extrapancreatic insulin-producing cells in multiple organs in diabetes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[16]  S. Ferber,et al.  New organs from our own tissues: liver-to-pancreas transdifferentiation , 2003, Trends in Endocrinology & Metabolism.

[17]  M. Grompe.  Pancreatic–hepatic switches in vivo , 2003, Mechanisms of Development.

[18]  E. Cerasi,et al.  Regulation of pdx-1 gene expression. , 2002, Diabetes.

[19]  B. Petersen,et al.  In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[20]  K. Zaret,et al.  A bipotential precursor population for pancreas and liver within the embryonic endoderm. , 2001, Development.

[21]  K. Zaret,et al.  Initiation of mammalian liver development from endoderm by fibroblast growth factors. , 1999, Science.

[22]  Yoshimitsu Yamasaki,et al.  PDX-1 and MafA play a crucial role in pancreatic beta-cell differentiation and maintenance of mature beta-cell function. , 2008, Endocrine journal.

[23]  Lung-Ji Chang,et al.  Reprogramming liver-stem WB cells into functional insulin-producing cells by persistent expression of Pdx1- and Pdx1-VP16 mediated by lentiviral vectors , 2006, Laboratory Investigation.

[24]  D. Melton,et al.  Role of endothelial cells in early pancreas and liver development , 2003, Mechanisms of Development.

[25]  I. Swenne,et al.  Growth Pattern of Pancreatic Islets in Animals , 1977 .