| Adult mouse intrahepatic biliary epithelial cells induced in vitro to become insulin-producing cells. | |
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MedLine Citation:
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PMID: 19168505 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Transdifferentiation of cells from a patient's own liver into pancreatic beta-cells could be useful for beta-cell replacement. We hypothesized that intrahepatic biliary epithelial cells (IHBECs) could become a new source of insulin-producing cells. IHBECs isolated from adult mice were expanded using our novel culture method termed, collagen-embedded floating culture method (CEFCM). With CEFCM, IHBECs formed three-dimensional ductal cysts and rapidly expanded their number by about 15-fold within 2 weeks. Over 90% of cells were positive for cytokeratin 7 and 19. At day 14, IHBECs were transfected with adenoviral (Ad)- pancreas duodenum homeobox 1 (Pdx-1), NeuroD or Pdx-1/VP16. After 7 additional days in serum- and insulin-free differentiation medium (DM), cell phenotypes were determined by RT-PCR, immunostaining and ELISA for insulin. In DM control IHBECs started to express some endocrine progenitor genes (Neurog3, NeuroD, Nkx6.1, and Pdx-1) but lacked insulin gene (Ins) mRNA. Transduced expression of PDX-1, NEUROD or PDX-1/VP16 led to expression of not only INS but also GLUT2 and prohormone convertase 1 and 2. About 3% of 4000 cells counted in PDX-1/VP16 transduced cultures stained strongly for C-peptide suggesting that a subpopulation may have the capacity for differentiation. Transduced cells released insulin (Ad-PDX-1 0.08+/-0.05, Ad-NEUROD 0.33+/-0.09, Ad-PDX-1/VP16 0.37+/-0.14 ng/1x10(5) cells after 48 h in culture). IHBECs can be markedly expanded, and then with molecular manipulation a subpopulation of these cells can differentiate towards a beta-cell phenotype. This approach may lead to a new source of beta-cells that can be used for transplantation in diabetes. |
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Authors:
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Masaki Nagaya; Hitoshi Katsuta; Hideaki Kaneto; Susan Bonner-Weir; Gordon C Weir |
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Publication Detail:
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Type: Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-01-23 |
Journal Detail:
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Title: The Journal of endocrinology Volume: 201 ISSN: 1479-6805 ISO Abbreviation: J. Endocrinol. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-03-26 Completed Date: 2009-07-23 Revised Date: 2011-06-01 |
Medline Journal Info:
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Nlm Unique ID: 0375363 Medline TA: J Endocrinol Country: England |
Other Details:
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Languages: eng Pagination: 37-47 Citation Subset: IM |
Affiliation:
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Research Division, Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Age Factors Animals Basic Helix-Loop-Helix Transcription Factors / genetics, metabolism Bile Ducts, Intrahepatic / cytology, metabolism, physiology* Cell Transdifferentiation / genetics* Cells, Cultured Epithelial Cells / metabolism, physiology* Gene Expression Profiling Herpes Simplex Virus Protein Vmw65 / genetics Homeodomain Proteins / genetics, metabolism Insulin / metabolism Insulin-Secreting Cells / metabolism, physiology* Male Mice Mice, Inbred C57BL Nerve Tissue Proteins / genetics, metabolism Trans-Activators / genetics, metabolism Transduction, Genetic* |
| Chemical | |
Reg. No./Substance:
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0/Basic Helix-Loop-Helix Transcription Factors; 0/Herpes Simplex Virus Protein Vmw65; 0/Homeodomain Proteins; 0/Nerve Tissue Proteins; 0/Trans-Activators; 0/pancreatic and duodenal homeobox 1 protein; 11061-68-0/Insulin; 169238-82-8/NeuroD protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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