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整合熔体静电纺丝书写技术和微流控技术,构建用于高保真药物筛选的人体心脏微环境。

Integrating melt electrospinning writing and microfluidics to engineer a human cardiac microenvironment for high-fidelity drug screening.

作者信息

Wang Yu-Hong, Liu Ting-Ting, Guo Yan-Ping, Zhu Shuo-Ji, Liao Zi-Ming, Song Jia-Mei, Zhu Xi-Ming, Liang Jia-Liang, Nasser Moussa Ide, Liu Nan-Bo, Chang De-Hua, Zhu Ping, Yao Bin

机构信息

Academy of Medical Engineering and Translational Medicine, Tianjin University, 300072, China.

Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510100, China.

出版信息

Bioact Mater. 2024 Dec 11;45:551-566. doi: 10.1016/j.bioactmat.2024.11.037. eCollection 2025 Mar.

Abstract

The preclinical evaluation of drug-induced cardiotoxicity is critical for developing novel drug, helping to avoid drug wastage and post-marketing withdrawal. Although human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and the engineered heart organoid have been used for drug screening and mimicking disease models, they are always limited by the immaturity and lack of functionality of the cardiomyocytes. In this study, we constructed a Cardiomyocytes-on-a-Chip (CoC) that combines micro-grooves (MGs) and circulating mechanical stimulation to recapitulate the well-organized structure and stable beating of myocardial tissue. The phenotypic changes and maturation of CMs cultured on the CoC have been verified and can be used for the evaluation of cardiotoxicity and cardioprotective drug responses. Taken together, these results highlight the ability of our myocardial microarray platform to accurately reflect clinical behaviour, underscoring its potential as a powerful pre-clinical tool for assessing drug response and toxicity.

摘要

药物诱导的心脏毒性的临床前评估对于开发新药至关重要,有助于避免药物浪费和上市后撤市。尽管人诱导多能干细胞衍生的心肌细胞(iPSC-CMs)和工程化心脏类器官已用于药物筛选和模拟疾病模型,但它们总是受到心肌细胞不成熟和功能缺乏的限制。在本研究中,我们构建了一种芯片上的心肌细胞(CoC),它结合了微槽(MGs)和循环机械刺激,以重现心肌组织的组织结构良好和稳定跳动。在CoC上培养的心肌细胞的表型变化和成熟已得到验证,可用于评估心脏毒性和心脏保护药物反应。综上所述,这些结果突出了我们的心肌微阵列平台准确反映临床行为的能力,强调了其作为评估药物反应和毒性的强大临床前工具的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2de1/11696762/7ceb4b51331f/ga1.jpg

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