Ex Vivo Tumor‐on‐a‐Chip Platforms to Study Intercellular Interactions within the Tumor Microenvironment

Kumar, Vardhman; Varghese, Shyni

doi:10.1002/adhm.201801198

Cited by 56 publications

(46 citation statements)

References 129 publications

(167 reference statements)

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“…Until recently, most bioengineering models provided little insight into the role of the immune cells in the TME, with cancer research dominated by immunosuppressive in vivo models and mono-culture in vitro systems[180–183]. Due to the important role that the immune cells can play in cancer progression, recent models have attempted to mimic the native immune component of the TME[184–186]. Some of these models take advantage of patient’s peripheral blood mononuclear cells from which dendritic cells, lymphocytes, monocytes, or natural killer cells can be derived[187].…”

Section: Immune Interactions In the ‘Cancer-organ’ Modelsmentioning

confidence: 99%

Integrated cancer tissue engineering models for precision medicine

et al. 2019

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Tumors are not merely cancerous cells that undergo mindless proliferation. Rather, they are highly organized and interconnected organ systems. Tumor cells reside in complex microenvironments in which they are subjected to a variety of physical and chemical stimuli that influence cell behavior and ultimately the progression and maintenance of the tumor. As cancer bioengineers, it is our responsibility to create physiologic models that enable accurate understanding of the multi-dimensional structure, organization, and complex relationships in diverse tumor microenvironments. Such models can greatly expedite clinical discovery and translation by closely replicating the physiological conditions while maintaining high tunability and control of extrinsic factors. In this review, we discuss the current models that target key aspects of the tumor microenvironment and their role in cancer progression. In order to address sources of experimental variation and model limitations, we also make recommendations for methods to improve overall physiologic reproducibility, experimental repeatability, and rigor within the field. Improvements can be made through an enhanced emphasis on mathematical modeling, standardized in vitro model characterization, transparent reporting of methodologies, and designing experiments with physiological metrics. Taken together these considerations will enhance the relevance of in vitro tumor models, biological understanding, and accelerate treatment exploration ultimately leading to improved clinical outcomes. Moreover, the development of robust, user-friendly models that integrate important stimuli will allow for the in-depth study of tumors as they undergo progression from non-transformed primary cells to metastatic disease and facilitate translation to a wide variety of biological and clinical studies.

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Section: Immune Interactions In the ‘Cancer-organ’ Modelsmentioning

confidence: 99%

Integrated cancer tissue engineering models for precision medicine

et al. 2019

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“…Nevertheless, several mechanistic studies using in vitro and on‐chip platforms have been conducted to elucidate the effect of shear stress, interstitial flow, intratumoral pressure and other mechanical perturbations in tumor mechanotransduction. [ 163,466,469–475 ] In particular, abnormal blood flow through leaky, tortuous and looping tumor vasculature results in lower shear stress leading to poor diffusional transport and hypoxia. This in turn leads to selection of cells with higher invasion potential and survivability.…”

Section: Modeling Vascular Mechanopathology In Vascularized Microphysmentioning

confidence: 99%

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Pradhan

Banda

Farino

et al. 2020

Adv Healthcare Materials

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The vascular system is integral for maintaining organ‐specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue‐engineered constructs and microphysiological on‐chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ‐specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State‐of‐the‐art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ‐specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular‐parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.

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“…Dynamic 3D cultures include either cell free scaffold or scaffold-embedded cultured in bioreactors, or perfused in microfluidic devices (Table 1; Figure 2). [ [75][76][77][78] Organ-on-a-chip…”

Section: D Scaffold-free Systems-cells Spheroidsmentioning

confidence: 99%

“…This model has many advantages: more specifically, it allows a precise control of the microenvironment, continuous flow perfusion culture, and it is suitable for high-throughput applications. Additionally, it allows maintaining some of the main tumor microenvironment (TME) features present in vivo such as multicellular interactions, ECM-based biochemical properties (by using biomaterials to encapsulate the cells), biophysical signals and their gradients [128], hypoxia [129], and others [76].…”

Section: Organ-on-a Chipmentioning

confidence: 99%

Trends in Bone Metastasis Modeling

Laranga

Duchi

Ibrahim

et al. 2020

Cancers

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Bone is one of the most common sites for cancer metastasis. Bone tissue is composed by different kinds of cells that coexist in a coordinated balance. Due to the complexity of bone, it is impossible to capture the intricate interactions between cells under either physiological or pathological conditions. Hence, a variety of in vivo and in vitro approaches have been developed. Various models of tumor–bone diseases are routinely used to provide valuable information on the relationship between metastatic cancer cells and the bone tissue. Ideally, when modeling the metastasis of human cancers to bone, models would replicate the intra-tumor heterogeneity, as well as the genetic and phenotypic changes that occur with human cancers; such models would be scalable and reproducible to allow high-throughput investigation. Despite the continuous progress, there is still a lack of solid, amenable, and affordable models that are able to fully recapitulate the biological processes happening in vivo, permitting a correct interpretation of results. In the last decades, researchers have demonstrated that three-dimensional (3D) methods could be an innovative approach that lies between bi-dimensional (2D) models and animal models. Scientific evidence supports that the tumor microenvironment can be better reproduced in a 3D system than a 2D cell culture, and the 3D systems can be scaled up for drug screening in the same way as the 2D systems thanks to the current technologies developed. However, 3D models cannot completely recapitulate the inter- and intra-tumor heterogeneity found in patients. In contrast, ex vivo cultures of fragments of bone preserve key cell–cell and cell–matrix interactions and allow the study of bone cells in their natural 3D environment. Moreover, ex vivo bone organ cultures could be a better model to resemble the human pathogenic metastasis condition and useful tools to predict in vivo response to therapies. The aim of our review is to provide an overview of the current trends in bone metastasis modeling. By showing the existing in vitro and ex vivo systems, we aspire to contribute to broaden the knowledge on bone metastasis models and make these tools more appealing for further translational studies.

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Ex Vivo Tumor‐on‐a‐Chip Platforms to Study Intercellular Interactions within the Tumor Microenvironment

Cited by 56 publications

References 129 publications

Integrated cancer tissue engineering models for precision medicine

Integrated cancer tissue engineering models for precision medicine

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Trends in Bone Metastasis Modeling

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