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利用肝脏类器官作为模型研究罕见肝脏疾病的病理生物学

Using Liver Organoids as Models to Study the Pathobiology of Rare Liver Diseases.

作者信息

Obeid Dalia A, Mir Tanveer Ahmad, Alzhrani Alaa, Altuhami Abdullah, Shamma Talal, Ahmed Sana, Kazmi Shadab, Fujitsuka Iriya, Ikhlaq Mohd, Shabab Mohammad, Assiri Abdullah M, Broering Dieter C

机构信息

Tissue/Organ Bioengineering and BioMEMS Lab, Organ Transplant Centre of Excellence, Transplant Research and Innovation Department, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.

College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.

出版信息

Biomedicines. 2024 Feb 17;12(2):446. doi: 10.3390/biomedicines12020446.

Abstract

Liver organoids take advantage of several important features of pluripotent stem cells that self-assemble in a three-dimensional culture matrix and reproduce many aspects of the complex organization found within their native tissue or organ counterparts. Compared to other 2D or 3D in vitro models, organoids are widely believed to be genetically stable or docile structures that can be programmed to virtually recapitulate certain biological, physiological, or pathophysiological features of original tissues or organs in vitro. Therefore, organoids can be exploited as effective substitutes or miniaturized models for the study of the developmental mechanisms of rare liver diseases, drug discovery, the accurate evaluation of personalized drug responses, and regenerative medicine applications. However, the bioengineering of organoids currently faces many groundbreaking challenges, including a need for a reasonable tissue size, structured organization, vascularization, functional maturity, and reproducibility. In this review, we outlined basic methodologies and supplements to establish organoids and summarized recent technological advances for experimental liver biology. Finally, we discussed the therapeutic applications and current limitations.

摘要

肝脏类器官利用了多能干细胞的几个重要特性,这些细胞在三维培养基质中自组装,并重现其天然组织或器官对应物中复杂组织的许多方面。与其他二维或三维体外模型相比,人们普遍认为类器官是基因稳定或易于操控的结构,可以通过编程在体外几乎完全重现原始组织或器官的某些生物学、生理学或病理生理学特征。因此,类器官可作为有效的替代物或小型化模型,用于研究罕见肝脏疾病的发育机制、药物发现、准确评估个性化药物反应以及再生医学应用。然而,类器官的生物工程目前面临许多开创性挑战,包括需要合理的组织大小、结构化组织、血管化、功能成熟度和可重复性。在这篇综述中,我们概述了建立类器官的基本方法和补充材料,并总结了实验性肝脏生物学的最新技术进展。最后,我们讨论了其治疗应用和当前的局限性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b490/10887144/fc54a9033eee/biomedicines-12-00446-g001.jpg

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