Abstract
Organ on chip (OOC) has emerged as a major technological breakthrough and distinct model system revolutionizing biomedical research and drug discovery by recapitulating the crucial structural and functional complexity of human organs in vitro. OOC are rapidly emerging as powerful tools for oncology research. Indeed, Cancer on chip (COC) can ideally reproduce certain key aspects of the tumor microenvironment (TME), such as biochemical gradients and niche factors, dynamic cell–cell and cell–matrix interactions, and complex tissue structures composed of tumor and stromal cells. Here, we review the state of the art in COC models with a focus on the microphysiological systems that host multicellular 3D tissue engineering models and can help elucidate the complex biology of TME and cancer growth and progression. Finally, some examples of microengineered tumor models integrated with multi-organ microdevices to study disease progression in different tissues will be presented.
Highlights
The primary non-malignant stromal cells of the tumor microenvironment (TME) are cancer-associated fibroblasts (CAFs) and endothelial cells; both these cells actively interact with tumor cells, among themselves, and with the extra cellular matrix (ECM) by secreting chemokines, growth factors, enzymes, extracellular vesicles, and miRNAs that regulate the expression of genes and proteins which influence metabolic pathways associated with cancer [46]
Created a patient-specific glioblastoma on a chip by printing cells encapsulated in a brainderived decellularized extracellular matrix (BdECM) [104]. They created a Cancer on chip (COC) provided with a compartmentalized cancer-stroma structure; to mimic the heterogeneous ecology of a glioblastoma, they build their model by surrounding the cancerous tissue with microvessels and induce the formation of central hypoxia by fabricating a device composed of selectively gas-permeable parts
Our results demonstrated that such COC allowed to capture ECM dynamics and model drug delivery supporting scientists to evaluating the efficacy of such a treatment approach [2]
Summary
It is recognized that cancer cells are able to respond to environmental cues provided by TME [2] These conclusions sustain a drastic change in the way of conceiving the cancer: from a gene-centric to a dynamic disease featured by complex interactions between cancer cells and their environment [1,3]. Defining optimal in vitro tumor models to mimic the specificity of the TME seems to be of growing interest for the scientific community, demonstrated by the fact that during the last ten years, the number of publications on the topic increased exponentially [1,4] This is due to the recent progresses in developing many different new techniques that are potentially of great value in the context of 3D tumor models and tumor–TME interaction studies [5,6,7]. Due to the recent advances in coupling multiple human organ chips to create human body on chip models, the possibility of creating multiorgan models of the metastatic spread of cancer is currently under investigation [16,20,39,40,41,42]
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