An in vivo Like Micro-Carcinoma Model

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.

Paracrine Signaling from a Three-Dimensional Model of Bladder Carcinoma and from Normal Bladder Switch the Phenotype of Stromal Fibroblasts

“…Bladder specimens were obtained from pig bladders. The decellularization process was done following a previously described protocol [16][17][18][19], with the following modifications. The smooth muscle layer was removed by surgical delamination and was then cut into 1 cm 2 fragments.…”

“…We took advantage of a 3D in vitro system developed by our group based on natural decellularized organs of microscopic dimensions that conserve the micro-architecture and protein composition of the original organ [16][17][18] to recreate an in vitro carcinoma [19]. The purpose of this system is to recreate, much as possible, as the in vivo conditions where epithelial-stromal interactions are preserved in an in vitro system.…”

Assessment of Antitumor and Antiproliferative Efficacy and Detection of Protein‐Protein Interactions in Cancer Cells from 3D Tumor Spheroids

“…Although 3D spheroid formation has been reported mostly for breast, lung, and colon cancer cells, it has not been widely reported for Calu‐3 lung cancer cells because of their slow growth. Calu‐3 cell models have, however, been reported in a human airway model of inflammation and in organ‐on‐a‐chip (Camargo, Shamis, Assis, & Mitrani, 2019; Zhu, Chidekel, & Shaffer, 2010) and solid synthetic scaffold applications.…”