Adipose Stroma Induces Branching Morphogenesis of Engineered Epithelial Tubules

The mammary gland and other treelike organs develop their characteristic fractal geometries through branching morphogenesis, a process in which the epithelium bifurcates and invades into the surrounding stroma. Controlling the pattern of branching is critical for engineering these organs. In vivo ,...

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Bibliographic Details
Published in:Tissue engineering. Part A 2010-12, Vol.16 (12), p.3719-3726
Main Authors: Pavlovich, Amira L., Manivannan, Sriram, Nelson, Celeste M.
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Adipocytes - cytology
Adipocytes - physiology
Animals
Body fat
Breasts
Cell culture
Cell Differentiation - genetics
Cell Differentiation - physiology
Cell Line
Cellular biology
Epithelial cells
Epithelial Cells - cytology
Epithelial Cells - physiology
Fat cells
Female
Fluorescent Antibody Technique
Mammary Glands, Animal - cytology
Mice
Morphogenesis
Morphogenesis - genetics
Morphogenesis - physiology
Morphology
Original
Original Articles
Physiological aspects
Reverse Transcriptase Polymerase Chain Reaction
Tissue engineering
Tissue Engineering - methods
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Summary:The mammary gland and other treelike organs develop their characteristic fractal geometries through branching morphogenesis, a process in which the epithelium bifurcates and invades into the surrounding stroma. Controlling the pattern of branching is critical for engineering these organs. In vivo , the branching process is instructed by stromal–epithelial interactions and adipocytes form the largest component of the fatty stroma that surrounds the mammary epithelium. Here, we used microlithographic approaches to engineer a three-dimensional culture model that enables analysis of the effect of adipocytes on the pattern of branching morphogenesis of mammary epithelial cells. We found that adipocyte-rich stroma induces branching through paracrine signals, including hepatocyte growth factor, but does not affect the branching pattern per se . This tissue engineering approach can be expanded to other organs, and should enable piecemeal analysis of the cellular populations that control patterning during normal development.
ISSN:1937-3341
1937-335X
DOI:10.1089/ten.tea.2009.0836