Organotypic cancer tissue models for drug screening: 3D constructs, bioprinting and microfluidic chips

Radhakrishnan, Janani; Varadaraj, Sudha; Dash, Sanat Kumar; Sharma, Akriti; Verma, Rama Shanker

doi:10.1016/j.drudis.2020.03.002

Cited by 63 publications

(38 citation statements)

References 77 publications

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“…It has been reported that cancer cells tend to migrate towards the direction of liquid flow, and the microfluidic chip provides a mechanical force to mimic TME [37]. These merits allow 3D printing to enhance the function of microfluidic chips, and 3D printing gradually became an important method in cancer modeling and drug screening on chips [38][39][40][41]. Several representative studies on the use of 3D printed microfluidic device for cancer modeling or diagnosis in the past five years was summarized in Table 2.…”

Section: D Printed Microfluidic Chip and Cancer Modelsmentioning

confidence: 99%

Multifunctional microfluidic chip for cancer diagnosis and treatment

Guo¹,

Zhang²,

Liu³

et al. 2021

Nanotheranostics

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Microfluidic chip is not a chip in the traditional sense. It is technologies that control fluids at the micro level. As a burgeoning biochip, microfluidic chips integrate multiple disciplines, including physiology, pathology, cell biology, biophysics, engineering mechanics, mechanical design, materials science, and so on. The application of microfluidic chip has shown tremendous promise in the field of cancer therapy in the past three decades. Various types of cell and tissue cultures, including 2D cell culture, 3D cell culture and tissue organoid culture could be performed on microfluidic chips. Patient-derived cancer cells and tissues can be cultured on microfluidic chips in a visible, controllable, and high-throughput manner, which greatly advances the process of personalized medicine. Moreover, the functionality of microfluidic chip is greatly expanding due to the customizable nature. In this review, we introduce its application in developing cancer preclinical models, detecting cancer biomarkers, screening anti-cancer drugs, exploring tumor heterogeneity and producing nano-drugs. We highlight the functions and recent development of microfluidic chip to provide references for advancing cancer diagnosis and treatment.

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Section: D Printed Microfluidic Chip and Cancer Modelsmentioning

confidence: 99%

Multifunctional microfluidic chip for cancer diagnosis and treatment

Guo¹,

Zhang²,

Liu³

et al. 2021

Nanotheranostics

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“…An interesting number of OoC models simulating the human heart have been developed with different levels of complexity. Its main application is centered on the evaluation of the contractile and rhythmic functions [6,7,13,18,44,122]. The OoC application for heart reproduction can be a powerful tool in the preclinical evaluation of a drug, as it allows to connect the heart with the lungs and the liver and to detect toxic reactions that may be absent when the drug is assessed in an isolated tissue [1,11,65].…”

Section: Heart-on-a-chipmentioning

confidence: 99%

Organ-on-a-Chip systems for new drugs development

2021

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Research on alternatives to the use of animal models and cell cultures has led to the creation of organ-on-a-chip systems, in which organs and their physiological reactions to the presence of external stimuli are simulated. These systems could even replace the use of human beings as subjects for the study of drugs in clinical phases and have an impact on personalized therapies. Organ-on-a-chip technology present higher potential than traditional cell cultures for an appropriate prediction of functional impairments, appearance of adverse effects, the pharmacokinetic and toxicological profile and the efficacy of a drug. This potential is given by the possibility of placing different cell lines in a three-dimensional-arranged polymer piece and simulating and controlling specific conditions. Thus, the normal functioning of an organ, tissue, barrier, or physiological phenomenon can be simulated, as well as the interrelation between different systems. Furthermore, this alternative allows the study of physiological and pathophysiological processes. Its design combines different disciplines such as materials engineering, cell cultures, microfluidics and physiology, among others. This work presents the main considerations of OoC systems, the materials, methods and cell lines used for their design, and the conditions required for their proper functioning. Examples of applications and main challenges for the development of more robust systems are shown. This non-systematic review is intended to be a reference framework that facilitates research focused on the development of new OoC systems, as well as their use as alternatives in pharmacological, pharmacokinetic and toxicological studies.

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“…Also, β1 integrin-mediated PI3K activation overrides treatment-induced cell cycle arrest and apoptosis in various solid tumors [ 16 ]. As the specific crosstalk between a given cancer and its stroma varies for each cancer type and perhaps for each patient, in vitro models that better reflect the in vivo human environments and their heterogeneity may provide more accurate indications of patient outcome [ 17 , 18 ].…”

Section: Modeling Solid Tumors In Vitromentioning

confidence: 99%

“…The oxygen level close to arterioles is higher than in perisinusoidal regions [ 32 , 35 ]. The ECM produced by niche cells provides structural integrity and has a regulatory effect on niche-forming cells and HSCs [ 18 ]. The most abundant proteins are FN, collagens (COL) from I to XI, tenascin, osteopontin, thrombospondin or elastin.…”

Section: Bone Marrow Microenvironment Home Of Hematological Maligmentioning

confidence: 99%

In Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?

Clara-Trujillo

Ferrer

Ribelles

2020

IJMS

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In hematological malignancies, leukemias or myelomas, malignant cells present bone marrow (BM) homing, in which the niche contributes to tumor development and drug resistance. BM architecture, cellular and molecular composition and interactions define differential microenvironments that govern cell fate under physiological and pathological conditions and serve as a reference for the native biological landscape to be replicated in engineered platforms attempting to reproduce blood cancer behavior. This review summarizes the different models used to efficiently reproduce certain aspects of BM in vitro; however, they still lack the complexity of this tissue, which is relevant for fundamental aspects such as drug resistance development in multiple myeloma. Extracellular matrix composition, material topography, vascularization, cellular composition or stemness vs. differentiation balance are discussed as variables that could be rationally defined in tissue engineering approaches for achieving more relevant in vitro models. Fully humanized platforms closely resembling natural interactions still remain challenging and the question of to what extent accurate tissue complexity reproduction is essential to reliably predict drug responses is controversial. However, the contributions of these approaches to the fundamental knowledge of non-solid tumor biology, its regulation by niches, and the advance of personalized medicine are unquestionable.

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Organotypic cancer tissue models for drug screening: 3D constructs, bioprinting and microfluidic chips

Cited by 63 publications

References 77 publications

Multifunctional microfluidic chip for cancer diagnosis and treatment

Multifunctional microfluidic chip for cancer diagnosis and treatment

Organ-on-a-Chip systems for new drugs development

In Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?

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