A Multifunctional 3D Co-Culture System for Studies of Mammary Tissue Morphogenesis and Stem Cell Biology
A Multifunctional 3D Co-Culture System for Studies of Mammary Tissue Morphogenesis and Stem Cell Biology
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DOI：
10.1371/journal.pone.0025661
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发表时间：
2011-09-30
期刊：
影响因子：
3.7
通讯作者：
Watson, Christine J.
中科院分区：
文献类型：
--
作者：
Campbell, Jonathan J.;Davidenko, Natalia;Watson, Christine J.
干细胞生态位和癌症治疗效果的研究需要复杂的多细胞结构以及不同类型的细胞和细胞外基质(ECM)在三维空间中的相互作用。我们设计了一个三维乳腺体外模型，它包含了一个明确的、多孔的胶原/透明质酸(HA)支架，形成了上皮细胞和脂肪细胞共培养的生理基础。在这种支架内形成极化的导管和腺泡结构，在没有重组基底膜(RBM)水凝胶的情况下概括了正常的组织形态。此外，胶原蛋白与透明质酸的比例可以控制类器官的发育结果，较高的透明质酸浓度有利于腺泡形态的发育。重要的是，这种培养系统概括了干细胞的生态位，因为原始乳腺干细胞形成了复杂的有机体，强调了这种方法在使用转基因动物或人类活检材料进行发育和肿瘤研究以及为个性化药物筛选癌症治疗方法方面的实用性。
Studies on the stem cell niche and the efficacy of cancer therapeutics require complex multicellular structures and interactions between different cell types and extracellular matrix (ECM) in three dimensional (3D) space. We have engineered a 3D in vitro model of mammary gland that encompasses a defined, porous collagen/hyaluronic acid (HA) scaffold forming a physiologically relevant foundation for epithelial and adipocyte co-culture. Polarized ductal and acinar structures form within this scaffold recapitulating normal tissue morphology in the absence of reconstituted basement membrane (rBM) hydrogel. Furthermore, organoid developmental outcome can be controlled by the ratio of collagen to HA, with a higher HA concentration favouring acinar morphological development. Importantly, this culture system recapitulates the stem cell niche as primary mammary stem cells form complex organoids, emphasising the utility of this approach for developmental and tumorigenic studies using genetically altered animals or human biopsy material, and for screening cancer therapeutics for personalised medicine.