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胆汁采集在改进基于细胞的肝功能检测中的前景

Prospect of Bile Fluids Collection in Improving Cell-Based Assay of Liver Function.

作者信息

Rizki-Safitri Astia, Tokito Fumiya, Nishikawa Masaki, Tanaka Minoru, Maeda Kazuya, Kusuhara Hiroyuki, Sakai Yasuyuki

机构信息

Department of Chemical System Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.

Laboratory of Stem Cell Regulation, Institute for Quantitative Biosciences (IQB), The University of Tokyo, Tokyo, Japan.

出版信息

Front Toxicol. 2021 Jun 3;3:657432. doi: 10.3389/ftox.2021.657432. eCollection 2021.

Abstract

The liver plays a pivotal role in the clearance of drugs. Reliable assays for liver function are crucial for various metabolism investigation, including toxicity, disease, and pre-clinical testing for drug development. Bile is an aqueous secretion of a functioning liver. Analyses of bile are used to explain drug clearance and related effects and are thus important for toxicology and pharmacokinetic research. Bile fluids collection is extensively performed , whereas this process is rarely reproduced as in the studies. The key to success is the technology involved, which needs to satisfy multiple criteria. To ensure the accuracy of subsequent chemical analyses, certain amounts of bile are needed. Additionally, non-invasive and continuous collections are preferable in view of cell culture. In this review, we summarize recent progress and limitations in the field. We highlight attempts to develop advanced liver cultures for bile fluids collection, including methods to stimulate the secretion of bile . With these strategies, researchers have used a variety of cell sources, extracellular matrix proteins, and growth factors to investigate different cell-culture environments, including three-dimensional spheroids, cocultures, and microfluidic devices. Effective combinations of expertise and technology have the potential to overcome these obstacles to achieve reliable bile assay systems.

摘要

肝脏在药物清除过程中起着关键作用。可靠的肝功能检测对于各种代谢研究至关重要,包括毒性、疾病以及药物开发的临床前测试。胆汁是正常肝脏分泌的水性液体。胆汁分析用于解释药物清除及相关效应,因此对毒理学和药代动力学研究很重要。胆汁收集操作广泛开展,但该过程很少能像研究中那样被重复。成功的关键在于所涉及的技术,这需要满足多个标准。为确保后续化学分析的准确性,需要一定量的胆汁。此外,考虑到细胞培养,非侵入性和连续性收集更为可取。在本综述中,我们总结了该领域的最新进展和局限性。我们重点介绍了为收集胆汁而开发先进肝脏培养技术的尝试,包括刺激胆汁分泌的方法。通过这些策略,研究人员利用了多种细胞来源、细胞外基质蛋白和生长因子来研究不同的细胞培养环境,包括三维球体、共培养和微流控装置。专业知识和技术的有效结合有可能克服这些障碍,以实现可靠的胆汁检测系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8fa/8915818/ae04a1a360f5/ftox-03-657432-g0001.jpg

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