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Z. Xu



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    MINI 22 - New Technology (ID 134)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI22.07 - An in Vitro Biomimetic Multi-Organ Microfluidic Chip System to Test Lung Cancer Metastasis (ID 1144)

      17:20 - 17:25  |  Author(s): Z. Xu

      • Abstract
      • Slides

      Background:
      Lung cancer is the leading cause of cancer mortality worldwide, and metastatic spread of cancer to distant organs is the main reason for lung cancer deaths. They spread to different distant organs, exhibit an outstandingly different situation of clinical characteristics and will be medically and surgically incurable. Thus, there is a clear need for a reliable and efficient in vitro culture model to enable transition to invasion and journey to distant organs of these critical steps in cancer metastatic progression.

      Methods:
      Here we report a biomimetic multi-organ microfluidic chip system more closely reconstituting the structural tissue arrangements, functional complexity and dynamic mechanical microenvironments and reproducing survival, growth, transition to invasion and journey to distant multi organs in lung cancer metastasis. To reconstitute the actual growth conditions of lung cancer in vivo, we created a thin, porous, flexible membrane, integrated microfluidic chip emulating the in vivo tissue structure and enabling heterotypic cell interactions, while maintaining cell compart-mentalization. The human bronchial epithelial cells and stromal cells were cultured on opposite sides of the membrane. Once the cells were grown to confluence, air was introduced into the epithelial compartment to create an air-liquid interface and more precisely mimic the lining of the lung air space. Then lung cancer cells were cultured on the human epithelial compartment to mimic lung cancer formation and the multi organ chambers were linked with side channels that supply lung cancer cells to the brain, bone or liver cells chamber to mimic lung cancer metastasis. In addition, the system provided analyzing cell physiology and visualizing complex cell behaviors in a more physiologically relevant context.

      Results:
      A biomimetic multi-organ microfluidic chip system was created. The quick formation of lung cancer cells that grow away from their natural margins and then attack adjacent components and spread to other organs were observed at all times and the cells characterizations were also detected accurately and effectively. In this multi-organ pathogenesis system, it might be possible to provide an ultrahigh level of reproducibility, authenticity and sensitivity.

      Conclusion:
      This microdevice provides a proof of principlefor this novel biomimetic strategy that is inspired by the integrated chemical, biological, and mechanical structures and functions of the living multi organs. This versatile system enables direct visualization and quantitative analysis of diverse biological processes of the intact lung cancer metastasis in ways that have not been possible in traditional cell culture or animal models.

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