A complex 3D human tissue culture system based on mammary stromal cells and silk scaffolds for modeling breast morphogenesis and function
Open accessAbstract
Epithelial-stromal interactions play a crucial role in normal embryonic development and carcinogenesis of the human breast while the underlying mechanisms of these events remain poorly understood. To address this issue, we constructed a physiologically relevant, three-dimensional (3D) culture surrogate of complex human breast tissue that included a tri-culture system made up of human mammary epithelial cells (MCF10A), human fibroblasts and adipocytes, i.e., the two dominant breast stromal cell types, in a Matrigel/collagen mixture on porous silk protein scaffolds. The presence of stromal cells inhibited MCF10A cell proliferation and induced both alveolar and ductal morphogenesis and enhanced casein expression. In contrast to the immature polarity exhibited by co-cultures with either fibroblasts or adipocytes, the alveolar structures formed by the tri-cultures exhibited proper polarity similar to that observed in breast tissue in vivo. Only alveolar structures with reverted polarity were observed in MCF10A monocultures. Consistent with their phenotypic appearance, more functional differentiation of epithelial cells was also observed in the tri-cultures, where casein alpha- and -beta mRNA expression was significantly increased. This in vitro tri-culture breast tissue system sustained on silk scaffold effectively represents a more physiologically relevant 3D microenvironment for mammary epithelial cells and stromal cells than either co-cultures or monocultures. This experimental model provides an important first step for bioengineering an informative human breast tissue system, with which to study normal breast morphogenesis and neoplastic transformation.
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Wang et al. designed a 3D tricellular composite that more accurately replicates human breast tissue than both co-cultures and monocultures by encapsulating human mammary epithelial cells, human fibroblasts, and adipocytes in a Matrigel-collagen gel.
“Wang et al . designed a 3D tricellular composite that more accurately replicates human breast tissue than both co-cultures and monocultures by encapsulating human mammary epithelial cells, human fibroblasts, and adipocytes in a Matrigel-collagen gel. 32”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [32]
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- Authors
- Wang, X., Sun, L., Maffini, M. V., Soto, A., Sonnenschein, C., & Kaplan, D. L.
- Affiliations
- Tufts University (US)
- Corresponding author
- Kaplan, David L.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 31
- Issue
- 14
- Pages
- 3920-3929
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC2847607
- OpenAlex
- W1978861648
- Cited by
- 120
- References
- 46
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 8 · 2018: 9 · 2017: 7 · 2016: 19 · 2015: 7 · 2014: 12 · 2013: 10 · 2012: 4
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Philip Morris International
- National Institutes of Health (EB002520)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- stromal-epithelial interactions, mammary stromal cells, 3D cell culture, MCF10A cells, fibroblasts, adipocytes, ductal morphogenesis, epithelial polarity, breast cancer
- MeSH terms
- Caseins, Cell Differentiation, Cell Line, Cell Survival, DNA, Epithelial Cells, Gene Expression Regulation, Humans, Models, Biological, Morphogenesis, RNA, Messenger, Cell Polarity, Stromal Cells, Mammary Glands, Human, Tissue Culture Techniques, Silk, Cell Shape, Cell Proliferation, Tissue Scaffolds
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