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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
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