在flk-1-knockout仿真小鼠中,通过胚胎细胞补充生成的驻留巨细胞的衍生和瘤微环境的构建
Satoko Ishii1, Kazuto Yamazaki2, Peng Li3
1Tsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3, Tokodai, Tsukuba, Ibaraki, 300-2635, Japan. s4-ishii@hhc.eisai.co.jp.
Scientific reports
|July 29, 2025
概括
这项研究证明了使用胚胎细胞细胞补充在物种内化学小鼠中构建瘤微环境. 来自捐赠者的细胞形成了关键组成部分,为先进的癌症模型铺平了道路.
科学领域:
- 在瘤学瘤学.
- 发展生物学 发展生物学
- 免疫学 免疫学 免疫学
背景情况:
- 瘤微环境 (TME) 极大地影响癌症的进展和治疗耐药性.
- 目前的人性化小鼠模型无法充分复制TME.
- 胚胎细胞补充为TME复制提供了一个有希望的策略,但跨物种应用仍然具有挑战性.
研究的目的:
- 建立一个基础的物种内仿真老鼠模型,用于构建由捐赠者衍生的TME.
- 为了验证胚胎细胞的补充,以产生功能性TME组件.
主要方法:
- 通过注入Azami-Green (AG) 阳性小鼠胚胎干细胞 (ESCs) 进入Flk-1淘汰胚胎来产生仿真小鼠.
- 对捐赠细胞对血管内皮细胞,造血细胞和巨细胞的贡献进行分析.
- 合成性瘤的植入和瘤透免疫细胞和 stromal 组件的表征.
主要成果:
- 在嵌合体小鼠中,注射的AG阳性ESC成功分化为血管内皮细胞,造血细胞和组织居民巨细胞.
- 嵌合体内的瘤微环境含有来自供体的淋巴细胞,巨细胞和血管内皮细胞.
- 来自捐赠者的CD8+T细胞表现出与野生类型对照细胞具有可比的细胞毒性活性.
结论:
- 这种物种内化学模型成功地证明了通过胚胎细胞补充来构建由供体衍生的TME.
- 该模型是TME生物学基础研究的宝贵工具.
- 这种方法在未来开发人性化的模型方面具有重大潜力,以推进临床前抗癌药物开发.
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