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从芯片上肝脏平台获得的经验教训。

Lessons Learned from Liver-on-Chip Platform.

作者信息

Razavi Zahra Sadat, Razavi Fateme Sadat, Soltani Madjid, Pazoki-Toroudi Hamidreza, Farokhi Simin, Azimi Iraj, Ahmadi Nahid

机构信息

Physiology Research Center, Iran University Medical Sciences, Tehran, Iran.

Biochemistry Research Center, Iran University Medical Sciences, Tehran, Iran.

出版信息

Ann Biomed Eng. 2025 Jun 28. doi: 10.1007/s10439-025-03779-y.

Abstract

The liver is one of the most studied human organs due to its central role in the metabolism of xenobiotics and pharmaceuticals. In vitro liver models that can mimic liver activities for the goal of studying pathophysiological hints in high-throughput and repeatable conditions have received a lot of attention during the past few decades. Two-dimensional (2D) models have been widely used in the process of screening potentially dangerous substances; nevertheless, these models have been unable to accurately depict the hepatic milieu's three-dimensionality (3D). To get around these limitations, scientists have developed better strategies for three-dimensional culturing that mimic the liver's natural milieu. The major goal of these models is to replicate the structure of the liver. They think about the interplay between parenchymal and nonparenchymal cells and the cellular environment. Newer models of the liver, called livers on a chip (LioCs), have been developed with the intention of simulating physiological fluid flow and, hence, performing key hepatic activities. This was done to ensure normal fluid dynamics. Due to their unrivaled capacity to recapture crucial aspects of the cellular microenvironment of the liver, LioC have been widely utilized in pathophysiology modeling. LioCs are now being used in tissue engineering and drug screening, where they have proven to be an effective tool. From 2D hepatocyte models, which are commonly used for liver toxicity screening, to more recent 3D and LioCs culture strategies, which have been adopted to mimic a more physiological microenvironment in order to study liver diseases, we discuss the development of experimental liver models in this article.

摘要

由于肝脏在异生物素和药物代谢中发挥核心作用,它是研究最多的人体器官之一。在过去几十年里,能够在高通量和可重复条件下模拟肝脏活动以研究病理生理线索的体外肝脏模型受到了广泛关注。二维(2D)模型在筛选潜在危险物质的过程中得到了广泛应用;然而,这些模型无法准确描绘肝脏微环境的三维特性(3D)。为了克服这些局限性,科学家们开发了更好的三维培养策略来模拟肝脏的自然微环境。这些模型的主要目标是复制肝脏的结构。它们考虑实质细胞和非实质细胞之间的相互作用以及细胞环境。一种名为芯片上的肝脏(LioC)的新型肝脏模型已经被开发出来,旨在模拟生理流体流动,从而执行关键的肝脏活动。这样做是为了确保正常的流体动力学。由于LioC具有无与伦比的能力来重现肝脏细胞微环境的关键方面,它们已被广泛应用于病理生理学建模。LioC目前正用于组织工程和药物筛选,并且已被证明是一种有效的工具。从常用于肝脏毒性筛选的二维肝细胞模型,到为了模拟更生理化的微环境以研究肝脏疾病而采用的最新三维和LioC培养策略,我们在本文中讨论实验性肝脏模型的发展。

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