Document Detail


Transdifferentiation of human islets to pancreatic ductal cells in collagen matrix culture.
MedLine Citation:
PMID:  8921586     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transdifferentiation is a change from one differentiated phenotype to another, involving morphological and functional phenotypic markers. Stability of the cellular phenotype is probably related to the extracellular milieu, as well as cytoplasmic and nuclear components that interact to control gene expression, and the conversion of cell phenotype is likely to be accomplished by selective enhancement of gene expression, which controls the terminal developmental commitment of cells. In this paper, we show the induction of cultured human islets cells to alter their usual phenotypic expression and attain morphological and functional characteristics of duct cells. Islets were isolated by collagenase digestion of pancreata that were removed from cadaveric organ donors. The islets were purified on a two-step density gradient of bovine serum albumin and were then placed into a three-dimensional rat-tail collagen gel matrix supplemented with NuSerum epithelial growth factor and cholera toxin. During the initial 96 h of culture, the islets underwent a cystic transformation that was associated with (1) the maintenance of immunoreactivity for neuron-specific enolase, an endocrine cell marker, but a progressive loss of insulin gene expression, (2) a loss of immunoreactivity for insulin protein, and (3) the appearance of CK-19, a marker for ductal cells. After the transformation was complete, the cells had the ultrastructural appearance of primitive duct-like cells. Cyst enlargement after the initial 96 h was associated, at least in part, with cell replication, as reflected in the 1500% increase in the incorporation of tritiated thymidine. These experiments are consistent with the transdifferentiation of an islet cell to a ductal cell. The exact mechanisms involved still need to be fully elucidated.
Authors:
S Yuan; L Rosenberg; S Paraskevas; D Agapitos; W P Duguid
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Differentiation; research in biological diversity     Volume:  61     ISSN:  0301-4681     ISO Abbreviation:  Differentiation     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1996-12-26     Completed Date:  1996-12-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0401650     Medline TA:  Differentiation     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  67-75     Citation Subset:  IM    
Affiliation:
Department of Pathology, McGill University, Montreal, Canada.
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MeSH Terms
Descriptor/Qualifier:
Autoradiography
Cell Differentiation / physiology
Cells, Cultured
Collagen / chemistry,  metabolism
Humans
Immunohistochemistry
Insulin / metabolism
Islets of Langerhans / cytology*,  metabolism
Microscopy
Pancreatic Ducts / cytology*
Phenotype
Thymidine / pharmacokinetics
Chemical
Reg. No./Substance:
11061-68-0/Insulin; 50-89-5/Thymidine; 9007-34-5/Collagen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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