bims-miftum 2020-07-26 papers

Issue of 2020–07–26
two papers selected by
Nidhi Menon, Virginia Tech

Sci Rep. 2020 Jul 21. 10(1): 12020

Cancer cells grown in 3D under fluid flow exhibit an aggressive phenotype and reduced responsiveness to the anti-cancer treatment doxorubicin.

Tayebeh Azimi, Marilena Loizidou, Miriam V Dwek.

3D laboratory models of cancer are designed to recapitulate the biochemical and biophysical characteristics of the tumour microenvironment and aim to enable studies of cancer, and new therapeutic modalities, in a physiologically-relevant manner. We have developed an in vitro 3D model comprising a central high-density mass of breast cancer cells surrounded by collagen type-1 and we incorporated fluid flow and pressure. We noted significant changes in cancer cell behaviour using this system. MDA-MB231 and SKBR3 breast cancer cells grown in 3D downregulated the proliferative marker Ki67 (P < 0.05) and exhibited decreased response to the chemotherapeutic agent doxorubicin (DOX) (P < 0.01). Mesenchymal markers snail and MMP14 were upregulated in cancer cells maintained in 3D (P < 0.001), cadherin-11 was downregulated (P < 0.001) and HER2 increased (P < 0.05). Cells maintained in 3D under fluid flow exhibited a further reduction in response to DOX (P < 0.05); HER2 and Ki67 levels were also attenuated. Fluid flow and pressure was associated with reduced cell viability and decreased expression levels of vimentin. In summary, aggressive cancer cell behaviour and reduced drug responsiveness was observed when breast cancer cells were maintained in 3D under fluid flow and pressure. These observations are relevant for future developments of 3D in vitro cancer models and organ-on-a-chip initiatives.

DOI: https://doi.org/10.1038/s41598-020-68999-9

Biomicrofluidics. 2020 Jul;14(4): 041501

Organ-on-a-chip engineering: Toward bridging the gap between lab and industry.

Qasem Ramadan, Mohammed Zourob.

Organ-on-a-chip (OOC) is a very ambitious emerging technology with a high potential to revolutionize many medical and industrial sectors, particularly in preclinical-to-clinical translation in the pharmaceutical arena. In vivo, the function of the organ(s) is orchestrated by a complex cellular structure and physiochemical factors within the extracellular matrix and secreted by various types of cells. The trend in in vitro modeling is to simplify the complex anatomy of the human organ(s) to the minimal essential cellular structure "micro-anatomy" instead of recapitulating the full cellular milieu that enables studying the absorption, metabolism, as well as the mechanistic investigation of drug compounds in a "systemic manner." However, in order to reflect the human physiology in vitro and hence to be able to bridge the gap between the in vivo and in vitro data, simplification should not compromise the physiological relevance. Engineering principles have long been applied to solve medical challenges, and at this stage of organ-on-a-chip technology development, the work of biomedical engineers, focusing on device engineering, is more important than ever to accelerate the technology transfer from the academic lab bench to specialized product development institutions and to the increasingly demanding market. In this paper, instead of presenting a narrative review of the literature, we systemically present a synthesis of the best available organ-on-a-chip technology from what is found, what has been achieved, and what yet needs to be done. We emphasized mainly on the requirements of a "good in vitro model that meets the industrial need" in terms of the structure (micro-anatomy), functions (micro-physiology), and characteristics of the device that hosts the biological model. Finally, we discuss the biological model-device integration supported by an example and the major challenges that delay the OOC technology transfer to the industry and recommended possible options to realize a functional organ-on-a-chip system.

DOI: https://doi.org/10.1063/5.0011583