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.
We present a three-dimensional model based on acellular scaffolds to recreate bladder carcinoma in vitro that closely describes the in vivo behavior of carcinoma cells. The integrity of the basement membrane and protein composition of the bladder scaffolds were examined by Laminin immunostaining and LC–MS/MS. Human primary bladder carcinoma cells were then grown on standard monolayer cultures and also seeded on the bladder scaffolds. Apparently, carcinoma cells adhered to the scaffold basement membrane and created a contiguous one-layer epithelium (engineered micro-carcinomas (EMCs)). Surprisingly, the gene expression pattern displayed by EMCs was similar to the profile expressed by the carcinoma cells cultured on plastic. However, the pattern of secreted growth factors was significantly different, as VEGF, FGF, and PIGF were secreted at higher levels by EMCs. We found that only the combination of factors secreted by EMCs, but not the carcinoma cells grown on plastic dishes, was able to induce either the pro-inflammatory phenotype or the myofibroblast phenotype depending on the concentration of the secreted factors. We found that the pro-inflammatory phenotype could be reversed. We propose a unique platform that allows one to decipher the paracrine signaling of bladder carcinoma and how this molecular signaling can switch the phenotypes of fibroblasts.
Background: Cell encapsulation technology is most likely the ultimate solution for cell therapy based clinical approaches. A key issue when developing a functional encapsulated construct is to consider not only the nature of the capsule but also how the cells should be incorporated into the capsule in order to minimally compromise their function. Methods: We have developed a tissue engineering approach, composed of decellularized micro scaffolds and various types of cells in which fully functional "Engineered Micro-Organs" (EMOs) are formed. Based on this technology, Engineered Micro-Pancreata (EMPs), made by seeding human islets into acellular micro-scaffolds, have been shown to remain viable, and to secrete high levels of insulin in a regulated manner as a function of glucose comparable to those secreted by fresh human islets in culture for long periods. We now report the development of a novel encapsulation approach that takes into account the structure and diffusion requirements of the encapsulated construct. Results: We here report the development of a capsule in which encapsulated EMPs, when implanted into xenogeneic mice, induced the formation of a fine vascular network and continued to secrete human insulin in a glucose regulated manner for several weeks.
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