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通过直接重编程获得的诱导肺上皮类细胞在小鼠中拯救流感病毒诱导的肺损伤

Tatsuya Kusumoto¹, Masaya Yotsukura², Takanori Asakura³

¹Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; Japan Society for the Promotion of Science, Tokyo, Japan.

Biochemical and biophysical research communications

|July 23, 2025

概括

研究人员使用含血清3D培养中的四种转录因子将纤维细胞重新编程成类似肺上皮细胞. 这些诱导的肺上皮状细胞 (iPULsSC) 对再生医学和治疗急性肺损伤有前途.

科学领域:

再生医学是一种再生医学.
干细胞生物学干细胞生物学
肺部生物学肺部生物学

背景情况:

身体细胞的直接重编程为产生特定细胞类型提供了一个有希望的途径.
之前的研究已经通过使用四种转录因子 (Nkx2-1,Foxa1,Foxa2,Gata6) 将小鼠胚胎纤维细胞 (MEFs) 无血清重编程为膜上皮样细胞.

研究的目的:

在含有血清的3D培养系统中生成诱导性肺上皮状细胞 (iPULsSC),使用相同的四个转录因子.
评估iPULsSC.的特性和治疗潜力.

主要方法:

使用含有血清的3D有机体培养系统.
使用四种转录因子 (Nkx2-1,Foxa1,Foxa2,Gata6) 的组合进行直接重编程.
分析了基因表达特征和细胞形态.
在急性肺损伤的小鼠模型中评估了体内治疗疗效.

主要成果:

在含有血清的介质中成功生成iPULsSC.
iPULsSC表现出与膜上皮细胞II型 (AT2) 和I型 (AT1) 细胞相似的全球基因表达特征.
表面活性蛋白 (SP) -C阳性iPULsSC表现出状体状结构,这是AT2细胞的特征.
在小鼠体内注射iPULsSC时,救助了流感病毒引起的急性肺损伤.

结论:

诱导性肺上皮状细胞 (iPULsSC) 可以在含有血清的3D培养物中有效生成.
iPULsSC 具有原生膜上皮细胞的关键特征,并显示出治疗潜力.
这种含血清的重编程方法为产生用于再生医学应用的肺上皮细胞提供了有价值的替代方案.

关键词:

膜上皮细胞是膜上皮细胞.细胞疗法是一种细胞疗法.直接进行重编程.流感是一次流感.表面活性蛋白 (SP) C

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