与代谢功能障碍相关的脂肪性肝病和脂肪性肝炎相关的肝癌临床前模型
Jack Leslie1, Kishore A Krishnamurthy2, Indresh K Gopalsamy3,4
1Newcastle Fibrosis Research Group, Bioscience Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Nature reviews. Gastroenterology & hepatology
|January 25, 2026
概括
本综述评估了代谢功能障碍相关的脂肪性肝病 (MASLD) 和其进展到肝癌的临床前模型. 它提出了一种标准化的方法,以确保这些模型准确地反映人类疾病,以获得更好的研究结果.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 翻译医学是一种翻译医学.
- 临床前研究 临床前研究
背景情况:
- 代谢功能障碍相关的脂肪性肝病 (MASLD) 和其严重形式,代谢功能障碍相关的脂肪性肝炎 (MASH),与纤维化,肝硬化和肝细胞癌 (HCC) 有关.
- 系统代谢功能障碍被认为是肝脏脂质积累和疾病进展的关键驱动因素.
- 准确的临床前模型对于理解MASLD和MASH-HCC的病理生理学以及开发有效的治疗方法至关重要.
研究的目的:
- 批判性地审查现有的MASLD和MASH-HCC的体内和体内临床前模型.
- 讨论各种模型的优点和局限性,包括转基因动物,人性化模型,有机体和芯片器官.
- 为临床前MASLD和MASH-HCC研究提出标准化管道,并促进对命名和验证的共识.
主要方法:
- 关于流行MASLD和MASH-HCC临床前模型的综合文献综述.
- 在体内模型 (转基因,人性化,大型动物) 和体外模型 (有机体,3D生物打印肝脏,精密切割肝脏切片,芯片上的器官,脱细胞化的支架) 的分析.
- 根据新的MASLD定义和标准化验证框架的建议重新评估证据.
主要成果:
- 确定了MASLD和MASH-HCC现有的各种临床前模型的优点和弱点.
- 强调需要模型,忠实地复制人类病理生理学特征.
- 引入了新的 in vitro 和先进的 in vivo 模型,这些模型有可能提高翻译相关性.
结论:
- 临床前模型的批判性评估对于推进MASLD和MASH-HCC研究至关重要.
- 需要一种标准化的方法和明确的验证标准,以确保实验模型的可靠性和翻译价值.
- 对实验设计的知情选择对于人类疾病的有意义的复制和成功的治疗开发至关重要.
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