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A liver-chip-based alcoholic liver disease model featuring multi-non-parenchymal cells

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Abstract

Non-parenchymal cells play a key role in the occurrence and development of alcoholic liver disease. However, this cellular behaviour has not been fully characterized, and it is inconvenient to observe in traditional in vitro alcoholic liver disease (ALD) models and animal models. Herein we developed a demountable liver-on-chip device for investigation of pathophysiological process of individual non-parenchymal cells in alcohol induced ALD. This liver-device comprised of HepG2, LX-2, EAhy926 and U937 cells, which were ordered in a physiological distribution under perfuse. This device allows improved HepG2 cells activities and maintained high liver functions which including albumin synthesis and urea secretion. This novel liver-device is able to recreate the damage process of hepatic non-parenchymal cell lines induced by alcohol, and to understand the intercellular communication between different types of hepatic cells during ALD by measuring multiple biomarkers of each types of hepatic non-parenchymal cell lines, including Ve-cadherin, eNOS, VEGF and α-SMA. The proposed liver-device is able to further studies of pathological analysis and drug- and toxicity-screening.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 21675017), the National Key Research and Development Program of China (No. SQ2017YFC170204-001), the Fundamental Research Funds for the Central Universities, China (No. DUT17LK25) and Sanming Project of Medicine in Shenzhen (No. SZSM201612049). We also thank Dr. Xiaorui Li and Dr. Yu Jin for helping supporting information collecting.

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Author notes

  1. J. Deng and Z. Z. Chen contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Fine Chemicals, Department of Chemical Engineering & School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China

    Jiu Deng, Yong Luo, Weijie Zhao & Bingcheng Lin

  2. Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China

    Zongzheng Chen & Zhengzhi Wu

  3. College of Pharmaceutical Science, Soochow University, Soochow, China

    Xiuli Zhang

  4. Biotechnologhy Division, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China

    Yao Lu & Bingcheng Lin

  5. College of Stomatology, Dalian Medical University, Dalian, China

    Tingjiao Liu

Authors
  1. Jiu Deng
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  2. Zongzheng Chen
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  3. Xiuli Zhang
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  4. Yong Luo
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  5. Zhengzhi Wu
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  6. Yao Lu
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  7. Tingjiao Liu
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  8. Weijie Zhao
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  9. Bingcheng Lin
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Contributions

J. Deng, Z.Z. Chen contributed equally to this work. Y. Luo, J. Deng, B.C. Lin, W.J. Zhao and X.L. Zhang designed the study; J. Deng, Z.Z. Chen and T.J. Liu performed the experiments; J. Deng, X.L. Zhang and Z.Z. Wu analyzed the data; J. Deng, Z.Z. Chen, Y. Luo, Y. Lu and B.C. Lin wrote the paper. All of the authors read and approved the final manuscript.

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Correspondence to Xiuli Zhang, Yong Luo or Bingcheng Lin.

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Deng, J., Chen, Z., Zhang, X. et al. A liver-chip-based alcoholic liver disease model featuring multi-non-parenchymal cells. Biomed Microdevices 21, 57 (2019). https://doi.org/10.1007/s10544-019-0414-9

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  • DOI: https://doi.org/10.1007/s10544-019-0414-9

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