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首页> 外文期刊>Biomaterials >A complex 3D human tissue culture system based on mammary stromal cells and silk scaffolds for modeling breast morphogenesis and function.
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A complex 3D human tissue culture system based on mammary stromal cells and silk scaffolds for modeling breast morphogenesis and function.

机译：基于乳腺基质细胞和丝绸支架的复杂3D人类组织培养系统，用于对乳房形态发生和功能进行建模。

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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.
机译：上皮-基质相互作用在人的正常胚胎发育和癌变过程中起着至关重要的作用，而对这些事件的潜在机制仍知之甚少。为解决此问题，我们构建了复杂的人乳腺组织的生理相关的三维（3D）培养替代物，其中包括由人乳腺上皮细胞（MCF10A），人成纤维细胞和脂肪细胞组成的三培养系统，即多孔丝蛋白支架上的基质胶/胶原混合物中，两种主要的乳腺基质细胞类型。基质细胞的存在抑制了MCF10A细胞的增殖，并诱导了肺泡和导管的形态发生，并增强了酪蛋白的表达。与成纤维细胞或脂肪细胞共培养显示的未成熟极性相反，由三培养形成的肺泡结构显示出与体内乳房组织中观察到的相似的正确极性。在MCF10A单培养中仅观察到极性反转的肺泡结构。与它们的表型一致，在三培养物中还观察到上皮细胞的更多功能分化，其中酪蛋白α-和-βmRNA表达显着增加。与共培养或单培养相比，这种在丝支架上维持的体外三培养乳腺组织系统有效地代表了乳腺上皮细胞和基质细胞在生理上更相关的3D微环境。该实验模型为生物工程信息性人体乳腺组织系统提供了重要的第一步，可用于研究正常的乳腺形态发生和肿瘤转化。

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