Dataset Information

High-Throughput Electromechanical Coupling Chip Systems for Real-Time 3D Invasion/Migration Assay of Cells.

ABSTRACT: Cell invasion/migration through three-dimensional (3D) tissues is not only essential for physiological/pathological processes, but a hallmark of cancer malignancy. However, how to quantify spatiotemporal dynamics of 3D cell migration/invasion is challenging. Here, this work reports a 3D cell invasion/migration assay (3D-CIMA) based on electromechanical coupling chip systems, which can monitor spatiotemporal dynamics of 3D cell invasion/migration in a real-time, label-free, nondestructive, and high-throughput way. In combination with 3D topological networks and complex impedance detection technology, this work shows that 3D-CIMA can quantitively characterize collective invasion/migration dynamics of cancer cells in 3D extracellular matrix (ECM) with controllable biophysical/biomechanical properties. More importantly, this work further reveals that it has the capability to not only carry out quantitative evaluation of anti-tumor drugs in 3D microenvironments that minimize the impact of cell culture dimensions, but also grade clinical cancer specimens. The proposed 3D-CIMA offers a new quantitative methodology for investigating cell interactions with 3D extracellular microenvironments, which has potential applications in various fields like mechanobiology, drug screening, and even precision medicine.

SUBMITTER: Jiang N

PROVIDER: S-EPMC10323643 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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High-Throughput Electromechanical Coupling Chip Systems for Real-Time 3D Invasion/Migration Assay of Cells.

Jiang Nan N Xu Liang L Han Yiming Y Wang Shuyi S Duan Xiaocen X Dai Jingyao J Hu Yunxing Y Liu Xiaozhi X Liu Zhiqiang Z Huang Jianyong J

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20230423 19

Cell invasion/migration through three-dimensional (3D) tissues is not only essential for physiological/pathological processes, but a hallmark of cancer malignancy. However, how to quantify spatiotemporal dynamics of 3D cell migration/invasion is challenging. Here, this work reports a 3D cell invasion/migration assay (3D-CIMA) based on electromechanical coupling chip systems, which can monitor spatiotemporal dynamics of 3D cell invasion/migration in a real-time, label-free, nondestructive, and hi ...[more]

PMID: 37088781

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Project description:RationaleOne goal of cardiac tissue engineering is the generation of a living, human pump in vitro that could replace animal models and eventually serve as an in vivo therapeutic. Models that replicate the geometrically complex structure of the heart, harboring chambers and large vessels with soft biomaterials, can be achieved using 3-dimensional bioprinting. Yet, inclusion of contiguous, living muscle to support pump function has not been achieved. This is largely due to the challenge of attaining high densities of cardiomyocytes-a notoriously nonproliferative cell type. An alternative strategy is to print with human induced pluripotent stem cells, which can proliferate to high densities and fill tissue spaces, and subsequently differentiate them into cardiomyocytes in situ.ObjectiveTo develop a bioink capable of promoting human induced pluripotent stem cell proliferation and cardiomyocyte differentiation to 3-dimensionally print electromechanically functional, chambered organoids composed of contiguous cardiac muscle.Methods and resultsWe optimized a photo-crosslinkable formulation of native ECM (extracellular matrix) proteins and used this bioink to 3-dimensionally print human induced pluripotent stem cell-laden structures with 2 chambers and a vessel inlet and outlet. After human induced pluripotent stem cells proliferated to a sufficient density, we differentiated the cells within the structure and demonstrated function of the resultant human chambered muscle pump. Human chambered muscle pumps demonstrated macroscale beating and continuous action potential propagation with responsiveness to drugs and pacing. The connected chambers allowed for perfusion and enabled replication of pressure/volume relationships fundamental to the study of heart function and remodeling with health and disease.ConclusionsThis advance represents a critical step toward generating macroscale tissues, akin to aggregate-based organoids, but with the critical advantage of harboring geometric structures essential to the pump function of cardiac muscle. Looking forward, human chambered organoids of this type might also serve as a test bed for cardiac medical devices and eventually lead to therapeutic tissue grafting.

Project description:Metastasis is the cause of most triple-negative breast cancer deaths, yet anti-metastatic therapeutics remain limited. To develop new therapeutics to prevent metastasis, pathophysiologically relevant assays that recapitulate tumor microenvironment is essential for disease modeling and drug discovery. Here, we have developed a microfluidic metastasis-on-chip assay of the early stages of cancer metastasis integrated with the triple-negative breast cancer cell line (MDA-MB-231), stromal fibroblasts and a perfused microvessel. High-content imaging with automated quantification methods was optimized to assess the tumor cell invasion and intravasation within the model. Cell invasion and intravasation were enhanced when fibroblasts co-cultured with a breast cancer cell line (MDA-MB-231). However, the non-invasive breast cancer cell line, MCF7, remained non-invasive in our model, even in the presence of fibroblasts. High-content screening of a targeted anti-cancer therapy drug library was conducted to evaluate the drug response sensitivity of the optimized model. Through this screening, we identified 30 compounds that reduced the tumor intravasation by 60% compared to controls. Multi-parametric phenotypic analysis was applied by combining the data from the metastasis-on-chip, cell proliferation and 2D cell migration screens, revealing that the drug library was clustered into eight distinct groups with similar drug responses. Notably, MEK inhibitors were enriched in cluster cell invasion and intravasation. In contrast, drugs with molecular targets: ABL, KIT, PDGF, SRC, and VEGFR were enriched in the drug clusters showing a strong effect on tumor cell intravasation with less impact on cell invasion or cell proliferation, of which, Imatinib, a multi-kinase inhibitor targeting BCR-ABL/PDGFR/KIT. Further experimental analysis showed that Imatinib enhanced endothelial barrier stability as measured by trans-endothelial electrical resistance and significantly reduced the trans-endothelial invasion activity of tumor cells. Our findings demonstrate the potential of our metastasis-on-chip assay as a powerful tool for studying cancer metastasis biology, drug discovery aims, and assessing drug responses, offering prospects for personalized anti-metastatic therapies for triple-negative breast cancer patients.

Dataset Information

High-Throughput Electromechanical Coupling Chip Systems for Real-Time 3D Invasion/Migration Assay of Cells.

Publications

High-Throughput Electromechanical Coupling Chip Systems for Real-Time 3D Invasion/Migration Assay of Cells.

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