Humanized mouse models in MDS

doi:10.1038/s41419-025-07861-0

2025-07-17

DOI：10.1038/s41419-025-07861-0

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骨髓增生异常综合征（MDS）是异质性造血干细胞疾病，其特征为无效造血、多系发育异常和进展为急性髓系白血病的风险。在识别复发性基因突变及其功能作用方面已取得进展，但将其转化为前临床模型仍具挑战性。传统的啮齿动物模型缺乏重现MDS病理生理学所必需的人类特异细胞因子支持和微环境支持。人源化小鼠模型，特别是整合了人类细胞因子（如MISTRG、NSG-SGM3、NOG-EXL）、免疫缺陷背景和共移植策略的模型，已改善了人类造血干细胞和祖细胞的植入及分化。这些模型允许体内研究克隆演化、突变特异性疾病动态及对治疗的反应。然而，仍存在长期植入受限、免疫重建不完全以及难以模拟早期或低风险MDS等困难。本文综述了当前适用于MDS研究的各类人源化和基因工程小鼠模型，评估其复制疾病复杂性、维持克隆结构和支撑转化研究的能力。我们强调了改进现有方法、开发新策略的必要性，并提出了未来标准化和提高临床相关性的方向。

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Cell Death and Disease

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9.6

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1.1W

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