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International
Journal of Bioprinting
RESEARCH ARTICLE
Distinct toxicity of microplastics/TBBPA
co-exposure to bioprinted liver organoids
derived from hiPSCs of healthy and
patient donors
Shaojun Liang , Yixue Luo , Yijun Su , Dawei Zhang , Shi-jie Wang ,
1
1†
1†
2
3
Mingen Xu , and Rui Yao *
4,5
1
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
(This article belongs to the Special Issue: Special Issue of International Journal of Bioprinting in the
BDMC 2023 Conference)
Abstract
† These authors contributed equally Bioprinted tissues derived from human-induced pluripotent stem cells (hiPSCs) can
to this work.
provide precise information on disease mechanisms and toxicity. The detection of
*Corresponding author: microplastics (MPs) in the liver tissues of patients with liver cirrhosis has raised
Rui Yao
(yaorui@tsinghua.edu.cn) concerns about their hepatotoxicity. MPs could absorb endocrine disruptors, such
as tetrabromobisphenol A (TBBPA) that is widely present in the environment,
Citation: Liang S, Luo Y, Su Y,
et al. Distinct toxicity of thereby complicating their toxic behaviors. To investigate their toxic mechanisms
microplastics/TBBPA co-exposure in liver tissues, we used the electro-assisted inkjet printing technology to fabricate
to bioprinted liver organoids healthy donor or patient-sourced hiPSC-derived Disse space organoids (DOs) that
derived from hiPSCs of healthy
and patient donors. Int J Bioprint. resembled the cell types and transcriptional features of Disse space. We observed
2024;10(3):1403. an accumulation of polystyrene MP microbeads in the DOs, and TBBPA exacerbated
doi: 10.36922/ijb.1403 the process. Neither MPs and TBBPA alone nor the co-exposure at non-cytotoxicity
Received: July 27, 2023 dosages could affect the liver functions of healthy donor hiPSC-derived DOs, as
Accepted: September 19, 2023 revealed by transcriptomic and biochemical analyses, whereas alcoholic liver
Published Online: January 18, 2024
disease (ALD) patient hiPSC-derived DOs exhibited the ALD disease transcriptional
Copyright: © 2024 Author(s). profiles. We found that MPs/TBBPA co-exposure significantly influenced the patient
This is an Open Access article organoids in terms of the pathological transcription expression and biochemical
distributed under the terms of the
Creative Commons Attribution profiles. These results suggested that both hereditary factors and pollutants
License, permitting distribution, contribute to susceptibility to environmental toxicants. This study exemplified
and reproduction in any medium, the value of bioprinting hiPSC-derived organoids in environmental toxicology,
provided the original work is
properly cited. offering a powerful strategy to advance the personalized environmental
toxicology paradigm.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional Keywords: Disse space organoids; Induced pluripotent stem cells; Bioprinting;
affiliations. Microplastics; Toxicology
Volume 10 Issue 3 (2024) 245 doi: 10.36922/ijb.1403

