Abstract
We here present a novel micro-system which allows to reconstitute an in vivo lung carcinoma where the various constituting epithelial and/or stromal structural and/or cellular components can be incorporated at will. In contrast to various “organs on a chip” the model is based on the observation that in nature, epithelial cells are always supported by a connective tissue or stroma. The model is based on acellular micro-scaffolds of microscopic dimensions which enable seeded cells to obtain gases and nutrients through diffusion thus avoiding the need for vascularization. As a proof of concept, we show that in this model, Calu-3 cells can form a well-organized, continuous, polarized, one-layer epithelium lining the stromal derived alveolar cavities, and express a different pattern of tumor-related genes than when grown as standard monolayer cultures on plastic culture dishes. To our knowledge, this model, introduces for the first time a system where the function of carcinogenic cells can be tested in vitro in an environment that closely mimics the natural in vivo situation.
Highlights
The intention of the model proposed here is to recreate as far as possible in an in vitro system, the in vivo conditions where normal epithelial stromal interactions are preserved
Epithelial cells are always supported by a connective tissue or stroma
Epithelial-stromal interactions must be necessary for homeostasis in any epithelial-containing organ
Summary
The intention of the model proposed here is to recreate as far as possible in an in vitro system, the in vivo conditions where normal epithelial stromal interactions are preserved. Epithelialstromal interactions are necessary for homeostasis in any epithelial-containing organ [1]. The tissue microarchitecture plays a main role in cell differentiation, organization, function, and molecular signaling, in normal conditions and in diseases such as cancer [1]. The interaction between parenchymal cells and their stroma is fundamental in determining the future of the epithelial cells [2]. In adult tissues two-way communication between cells and their surroundings is well established [3]. Some researchers have suggested that in tumors this cross-talk is disrupted and stroma could have a key role in carcinogenesis [4]
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