Document Detail


Self-renewal of embryonic-stem-cell-derived progenitors by organ-matched mesenchyme.
MedLine Citation:
PMID:  23041930     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
One goal of regenerative medicine, to use stem cells to replace cells lost by injury or disease, depends on producing an excess of the relevant cell for study or transplantation. To this end, the stepwise differentiation of stem cells into specialized derivatives has been successful for some cell types, but a major problem remains the inefficient conversion of cells from one stage of differentiation to the next. If specialized cells are to be produced in large numbers it will be necessary to expand progenitor cells, without differentiation, at some steps of the process. Using the pancreatic lineage as a model for embryonic-stem-cell differentiation, we demonstrate that this is a solvable problem. Co-culture with organ-matched mesenchyme permits proliferation and self-renewal of progenitors, without differentiation, and enables an expansion of more than a million-fold for human endodermal cells with full retention of their developmental potential. This effect is specific both to the mesenchymal cell and to the progenitor being amplified. Progenitors that have been serially expanded on mesenchyme give rise to glucose-sensing, insulin-secreting cells when transplanted in vivo. Theoretically, the identification of stage-specific renewal signals can be incorporated into any scheme for the efficient production of large numbers of differentiated cells from stem cells and may therefore have wide application in regenerative biology.
Authors:
Julie B Sneddon; Malgorzata Borowiak; Douglas A Melton
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-07
Journal Detail:
Title:  Nature     Volume:  491     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-29     Completed Date:  2013-01-16     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  765-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation / drug effects
Cell Division / drug effects
Cell Line
Coculture Techniques / methods*
Embryonic Stem Cells / cytology*,  drug effects,  metabolism
Endoderm / cytology*,  drug effects,  metabolism
Glucose / pharmacology
Humans
Insulin / metabolism
Male
Mesoderm / cytology*
Mice
Pancreas / cytology*
Pluripotent Stem Cells / cytology,  drug effects,  metabolism
Grant Support
ID/Acronym/Agency:
5 U42 RR006042-20/RR/NCRR NIH HHS; K08 DK084206/DK/NIDDK NIH HHS; K08 DK084206/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Insulin; IY9XDZ35W2/Glucose

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


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