title: A recapitulative three-dimensional model of breast carcinoma requires perfusion for multi-week growth.
abstract: Breast carcinomas are complex, three-dimensional tissues composed of cancer epithelial cells and stromal components, including fibroblasts and extracellular matrix. In vitro models that more faithfully recapitulate this dimensionality and stromal microenvironment should more accurately elucidate the processes driving carcinogenesis, tumor progression, and therapeutic response. Herein, novel in vitro breast carcinoma surrogates, distinguished by a relevant dimensionality and stromal microenvironment, are described and characterized. A perfusion bioreactor system was used to deliver medium to surrogates containing engineered microchannels and the effects of perfusion, medium composition, and the method of cell incorporation and density of initial cell seeding on the growth and morphology of surrogates were assessed. Perfused surrogates demonstrated significantly greater cell density and proliferation and were more histologically recapitulative of human breast carcinoma than surrogates maintained without perfusion. Although other parameters of the surrogate system, such as medium composition and cell seeding density, affected cell growth, perfusion was the most influential parameter.
authors: Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Kayla F
authors: KF
authors: Goliwas
authors: Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Lauren E
authors: LE
authors: Marshall
authors: Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Evette L
authors: EL
authors: Ransaw
authors: Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Joel L
authors: JL
authors: Berry
authors: Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Andra R
authors: AR
authors: Frost
keywords: Breast carcinoma; bioreactor; in vitro models; perfusion; three-dimensional; tumor microenvironment