Document Detail


In vitro cultivation of human islets from expanded ductal tissue.
MedLine Citation:
PMID:  10884429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A major obstacle to successful islet transplantation for both type 1 and 2 diabetes is an inadequate supply of insulin-producing tissue. This need for transplantable human islets has stimulated efforts to expand existing pancreatic islets and/or grow new ones. To test the hypothesis that human adult duct tissue could be expanded and differentiated in vitro to form islet cells, digested pancreatic tissue that is normally discarded from eight human islet isolations was cultured under conditions that allowed expansion of the ductal cells as a monolayer whereupon the cells were overlaid with a thin layer of Matrigel. With this manipulation, the monolayer of epithelial cells formed three-dimensional structures of ductal cysts from which 50-to 150- micrometer diameter islet-like clusters of pancreatic endocrine cells budded. Over 3-4 weeks culture the insulin content per flask increased 10- to 15-fold as the DNA content increased up to 7-fold. The cultivated human islet buds were shown by immunofluorescence to consist of cytokeratin 19-positive duct cells and hormone-positive islet cells. Double staining of insulin and non-beta cell hormones in occasional cells indicated immature cells still in the process of differentiation. Insulin secretion studies were done over 24 h in culture. Compared with their basal secretion at 5 mM glucose, cysts/cultivated human islet buds exposed to stimulatory 20 mM glucose had a 2.3-fold increase in secreted insulin. Thus, duct tissue from human pancreas can be expanded in culture and then be directed to differentiate into glucose responsive islet tissue in vitro. This approach may provide a potential new source of pancreatic islet cells for transplantation.
Authors:
S Bonner-Weir; M Taneja; G C Weir; K Tatarkiewicz; K H Song; A Sharma; J J O'Neil
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  97     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-08-10     Completed Date:  2000-08-10     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7999-8004     Citation Subset:  IM    
Affiliation:
Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA. susan.bonner-weir@joslin.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Cell Differentiation
Culture Techniques / methods*
Epithelial Cells / cytology
Humans
Insulin / secretion
Islets of Langerhans / cytology,  growth & development*
Middle Aged
Morphogenesis
Pancreatic Ducts / cytology,  growth & development*
Chemical
Reg. No./Substance:
0/Insulin
Comments/Corrections

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


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