AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.1403
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RESEARCH ARTICLE

Distinct toxicity of microplastics/TBBPA co-exposure to bioprinted liver organoids derived from hiPSCs of healthy and patient donors

Shaojun Liang1† ,  Yixue Luo1† ,  Yijun Su1 ,  Dawei Zhang2 ,  Shi-jie Wang3 ,  Mingen Xu4,5 ,  Rui Yao1*
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1 Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing, China
2 Senior Department of Infectious Diseases of the 5th Medical Center, PLA General Hospital, Beijing, China
3 National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China
4 Key Laboratory of Medical Information and 3D Biological of Zhejiang Province, Hangzhou Dianzi University, Hangzhou, China
5 Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
IJB, 1403 https://doi.org/10.36922/ijb.1403
Submitted: 27 July 2023 | Accepted: 19 September 2023 | Published: 18 January 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Bioprinted tissues derived from human-induced pluripotent stem cells (hiPSCs) can provide precise information on disease mechanisms and toxicity. The detection of microplastics (MPs) in the liver tissues of patients with liver cirrhosis has raised concerns about their hepatotoxicity. MPs could absorb endocrine disruptors, such as tetrabromobisphenol A (TBBPA) that is widely present in the environment, thereby complicating their toxic behaviors. To investigate their toxic mechanisms in liver tissues, we used the electro-assisted inkjet printing technology to fabricate healthy donor or patient-sourced hiPSC-derived Disse space organoids (DOs) that resembled the cell types and transcriptional features of Disse space. We observed an accumulation of polystyrene MP microbeads in the DOs, and TBBPA exacerbated the process. Neither MPs and TBBPA alone nor the co-exposure at non-cytotoxicity dosages could affect the liver functions of healthy donor hiPSC-derived DOs, as revealed by transcriptomic and biochemical analyses, whereas alcoholic liver disease (ALD) patient hiPSC-derived DOs exhibited the ALD disease transcriptional profiles. We found that MPs/TBBPA co-exposure significantly influenced the patient organoids in terms of the pathological transcription expression and biochemical profiles. These results suggested that both hereditary factors and pollutants contribute to susceptibility to environmental toxicants. This study exemplified the value of bioprinting hiPSC-derived organoids in environmental toxicology, offering a powerful strategy to advance the personalized environmental toxicology paradigm.

Keywords
Disse space organoids
Induced pluripotent stem cells
Bioprinting; Microplastics
Toxicology
Funding
The authors were sincerely grateful for funding from the National Key Research and Development Program of China (2022YFA1104600 and 2018YFA0109000).
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Conflict of interest
The authors declare no conflicts of interest.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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