Tissue-Engineered Bile Ducts for Disease Modeling and Therapy
Tissue-Engineered Bile Ducts for Disease Modeling and Therapy
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DOI：
10.1089/ten.tec.2020.0283
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发表时间：
2021-02-02
影响因子：
3
通讯作者：
Spee, Bart
中科院分区：
文献类型：
--
作者：
Wang, Zhenguo;Faria, Joao;Spee, Bart
在过去的几十年里，胆道组织工程得到了极大的关注，但目前有许多因素阻碍了这一领域的发展，最终形成了模拟体内生理并适合移植的生物工程胆管。本文就细胞来源的选择、生长因子和支架的影响、功能鉴定以及在胆管疾病模型和药物筛选中的应用等方面的最新进展作一综述。这篇综述适合广大读者，包括对胆管工程和疾病模型的现状和应用感兴趣的基础肝脏研究人员和临床医生。最近在胆管细胞体外培养和生物工程胆管组织生成方面的生物技术进展，在制造用于疾病建模、药物筛选和移植的胆管组织方面具有很高的潜力。在过去的几十年里，科学家们一直在寻找胆管细胞的来源，重点是原代胆管细胞或来源于肝细胞或干细胞的胆管细胞。同时，对胆道组织工程支架材料在胆道移植和胆道疾病模型中的应用进行了探索。本文就胆管细胞来源、信号分子和转录因子对细胞分化的影响、细胞外基质分子和支架在生物工程胆管组织中的作用及其在疾病模型和药物筛选中的应用等方面的研究进展作一综述。
Impact statementOver the past few decades, biliary tissue engineering has acquired significant attention, but currently a number of factors hinder this field to eventually generate bioengineered bile ducts that mimic in vivo physiology and are suitable for transplantation. In this review, we present the latest advances with respect to cell source selection, influence of growth factors and scaffolds, and functional characterization, as well as applications in cholangiopathy modeling and drug screening. This review is suited for a broad spectrum of readers, including fundamental liver researchers and clinicians with interest in the current state and application of bile duct engineering and disease modeling.Recent biotechnical advances in the in vitro culture of cholangiocytes and generation of bioengineered biliary tissue have a high potential for creating biliary tissue to be used for disease modeling, drug screening, and transplantation. For the past few decades, scientists have searched for a source of cholangiocytes, focused on primary cholangiocytes or cholangiocytes derived from hepatocytes or stem cells. At the same time, the development of scaffolds for biliary tissue engineering for transplantation and modeling of cholangiopathies has been explored. In this review, we provide an overview on the current understanding of cholangiocytes sources, the effect of signaling molecules, and transcription factors on cell differentiation, along with the effects of extracellular matrix molecules and scaffolds on bioengineered biliary tissues, and their application in disease modeling and drug screening.