Document Detail

Preadipocytes stimulate ductal morphogenesis and functional differentiation of human mammary epithelial cells on 3D silk scaffolds.
MedLine Citation:
PMID:  19338449     Owner:  NLM     Status:  MEDLINE    
Epithelial-mesenchymal interactions play an important role in regulating normal tissue development as well as tumor development for the mammary gland, but much is yet to uncover to reach a full understanding of their complexity. To address this issue, the establishment of relevant, surrogate, three-dimensional (3D) human tissue culture models is essential. In the present study, a novel 3D coculture system was developed to study the interactions between human mammary epithelial cells (MCF10A) and adipocytes, a prominent stromal cell type in native breast tissue. The MCF10A cells were cultured within a mixture of Matrigel and collagen in 3D porous silk scaffolds with or without predifferentiated human adipose-derived stem cells (hASCs). The presence of hASCs inhibited MCF10A cell proliferation, induced both alveolar and ductal morphogenesis, and enhanced their functional differentiation as evidenced by histology and functional analysis. The alveolar structures formed by cocultures exhibited proper, immature polarity when compared with native breast tissue. In contrast, only alveolar structures with reverted polarity were observed in the MCF10A monocultures. The effect of ductal morphogenesis in cocultures may correlate to hepatocyte growth factor secreted by the predifferentiated hASCs, based on results from a cytokine blocking assay. Taken together, this in vitro coculture model on silk scaffolds effectively reconstitutes a physiologically relevant 3D microenvironment for epithelial cells and stromal cells and provides a useful system to study tissue organization and epithelial morphogenesis in normal or diseased breast development.
Xiuli Wang; Xiaohui Zhang; Lin Sun; Balajikarthick Subramanian; Maricel V Maffini; Ana Soto; Carlos Sonnenschein; David L Kaplan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Tissue engineering. Part A     Volume:  15     ISSN:  1937-335X     ISO Abbreviation:  Tissue Eng Part A     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-08     Completed Date:  2009-12-23     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  101466659     Medline TA:  Tissue Eng Part A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3087-98     Citation Subset:  IM    
Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, USA.
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MeSH Terms
Adipocytes / cytology*,  metabolism
Cell Differentiation / physiology
Cell Line
Cell Proliferation
Cell Survival / physiology
Epithelial Cells / cytology*,  metabolism
Fibroins / chemistry*
Mammary Glands, Human / cytology*
Microscopy, Electron, Scanning
Reverse Transcriptase Polymerase Chain Reaction
Tissue Engineering / methods*
Tissue Scaffolds / chemistry*
Grant Support
Reg. No./Substance:

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