Human in vitro vascularized micro-organ and micro-tumor models are reproducible organ-on-a-chip platforms for studies of anticancer drugs

Liu, Yizhong; Sakolish, Courtney; Chen, Zunwei; Phan, Duc T. T.; Bender, R. Hugh F.; Hughes, Christopher C.W.; Rusyn, Ivan

doi:10.1016/j.tox.2020.152601

Cited by 29 publications

(22 citation statements)

References 46 publications

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“…The VLCCs formed had large stable vascular channels with capillary network structures between channels. This model is distinct from the vessellike structures developed by other groups [45]. Other models are flatter than full 3D models and cannot show angiogenesis sprouting from pre-existing blood vessels.…”

Section: Discussionmentioning

confidence: 51%

Three-Dimensional Vascularized Lung Cancer-on-a-Chip with Lung Extracellular Matrix Hydrogels for In Vitro Screening

Park

Kim

et al. 2021

Cancers

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Recent advances in immunotherapies and molecularly targeted therapies have led to an increased interest in exploring the field of in vitro tumor mimetic platforms. An increasing need to understand the mechanisms of anti-cancer therapies has led to the development of natural tumor tissue-like in vitro platforms capable of simulating the tumor microenvironment. The incorporation of vascular structures into the in vitro platforms could be a crucial factor for functional investigation of most anti-cancer therapies, including immunotherapies, which are closely related to the circulatory system. Decellularized lung extracellular matrix (ldECM), comprised of ECM components and pro-angiogenic factors, can initiate vascularization and is ideal for mimicking the natural microenvironment. In this study, we used a ldECM-based hydrogel to develop a 3D vascularized lung cancer-on-a-chip (VLCC). We specifically encapsulated tri-cellular spheroids made from A549 cells, HUVECs, and human lung fibroblasts, for simulating solid type lung cancer. Additionally, two channels were incorporated in the hydrogel construct to mimic perfusable vessel structures that resemble arterioles or venules. Our study highlights how a more effective dose-dependent action of the anti-cancer drug Doxorubicin was observed using a VLCC over 2D screening. This observation confirmed the potential of the VLCC as a 3D in vitro drug screening tool.

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Section: Discussionmentioning

confidence: 51%

Three-Dimensional Vascularized Lung Cancer-on-a-Chip with Lung Extracellular Matrix Hydrogels for In Vitro Screening

Park

Kim

et al. 2021

Cancers

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“…Liu et al [ 42 ] developed a microfluidic model for the seeding of cancer cells and the replication of the perfusable vascular networks surrounding the tumor. The anticancer drugs sorafenib, fluorouracil, and VCR were tested on the device on perfusable and non-perfusable colon cancer cultures.…”

Section: Resultsmentioning

confidence: 99%

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review

Gonçalves

Carvalho

Rodrigues

et al. 2022

Cancers

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The development of cancer models that rectify the simplicity of monolayer or static cell cultures physiologic microenvironment and, at the same time, replicate the human system more accurately than animal models has been a challenge in biomedical research. Organ-on-a-chip (OoC) devices are a solution that has been explored over the last decade. The combination of microfluidics and cell culture allows the design of a dynamic microenvironment suitable for the evaluation of treatments’ efficacy and effects, closer to the response observed in patients. This systematic review sums the studies from the last decade, where OoC with cancer cell cultures were used for drug screening assays. The studies were selected from three databases and analyzed following the research guidelines for systematic reviews proposed by PRISMA. In the selected studies, several types of cancer cells were evaluated, and the majority of treatments tested were standard chemotherapeutic drugs. Some studies reported higher drug resistance of the cultures on the OoC devices than on 2D cultures, which indicates the better resemblance to in vivo conditions of the former. Several studies also included the replication of the microvasculature or the combination of different cell cultures. The presence of vasculature can influence positively or negatively the drug efficacy since it contributes to a greater diffusion of the drug and also oxygen and nutrients. Co-cultures with liver cells contributed to the evaluation of the systemic toxicity of some drugs metabolites. Nevertheless, few studies used patient cells for the drug screening assays.

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“…This was exemplified in a colon cancer micro-tumor model perfused with the anticancer compounds fluorouracil, vincristine, and sorafenib compared with conventional monolayer cultures of endothelial or tumor cells. Results indicated that perfusable vascular networks are critical for drug safety evaluation, highlighting an additional challenge since this model better mimics the physiological microenvironment than 2-D cell cultures [131].…”

Section: Tumor Platformsmentioning

confidence: 99%

Multi-Organs-on-Chips for Testing Small-Molecule Drugs: Challenges and Perspectives

et al. 2021

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Organ-on-a-chip technology has been used in testing small-molecule drugs for screening potential therapeutics and regulatory protocols. The technology is expected to boost the development of novel therapies and accelerate the discovery of drug combinations in the coming years. This has led to the development of multi-organ-on-a-chip (MOC) for recapitulating various organs involved in the drug–body interactions. In this review, we discuss the current MOCs used in screening small-molecule drugs and then focus on the dynamic process of drug absorption, distribution, metabolism, and excretion. We also address appropriate materials used for MOCs at low cost and scale-up capacity suitable for high-performance analysis of drugs and commercial high-throughput screening platforms.

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Human in vitro vascularized micro-organ and micro-tumor models are reproducible organ-on-a-chip platforms for studies of anticancer drugs

Cited by 29 publications

References 46 publications

Three-Dimensional Vascularized Lung Cancer-on-a-Chip with Lung Extracellular Matrix Hydrogels for In Vitro Screening

Three-Dimensional Vascularized Lung Cancer-on-a-Chip with Lung Extracellular Matrix Hydrogels for In Vitro Screening

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review

Multi-Organs-on-Chips for Testing Small-Molecule Drugs: Challenges and Perspectives

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