鼠-鼠合体的骨髓含有多个肺细胞系的祖先
Enhong Li1, Bingqiang Wen1, Dengfeng Gao2
1Phoenix Children's Research Institute, Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, United States.
Frontiers in cell and developmental biology
|May 2, 2024
概括
骨髓移植可以增强,以修复癌症治疗后的肺损伤. 鼠-老鼠嵌合体产生了丰富的骨髓干细胞,可以再生肺细胞,为辐射诱导的肺损伤提供了新的治疗潜力.
科学领域:
- 再生医学是一种再生医学.
- 造血干细胞移植 造血干细胞移植
- 肺部生物学 肺部生物学
背景情况:
- 辐射诱导性肺损伤 (RILI) 是癌症治疗的重要并发症,影响肺的修复.
- 目前的骨髓 (BM) 移植策略在恢复肺组织的能力方面受到限制,原因是缺乏呼吸道原始体.
- 鼠-老鼠嵌合体提供了一种新的方法,以特定的祖先细胞丰富BM.
研究的目的:
- 调查来自老鼠-老鼠仿真体的BM在辐射引起的肺损伤后有助于肺部修复的潜力.
- 在丰富的BM种群中识别和表征新的呼吸道原生细胞.
- 在一个临床前模型中评估跨物种喜梅拉衍生的BM移植的治疗疗效.
主要方法:
- 通过胚胎囊注射创建老鼠-老鼠嵌合体,以用来自老鼠的祖先来丰富BM.
- 移植FACS分类的BM细胞从木乃伊到致命辐射的异构性小鼠.
- 通过免疫染,流细胞计和单细胞RNA测序 (scRNAseq) 来分析捐赠细胞对肺组织的贡献.
主要成果:
- 来自木乃伊的捐赠者BM细胞显示对所有肺内血造细胞的长期贡献.
- 在RILI后的肺内皮细胞和肺层细胞中观察到供体BM细胞的显著贡献 (高达8%).
- scRNAseq在模拟性BM中识别出独特的血管细胞样和介质细胞流体原始体种群,与正常BM不同.
结论:
- 鼠-老鼠仿真体产生丰富的BM,具有能够在RILI后为多种肺细胞类型作出贡献的新型原生种群.
- 这种方法证明了跨物种金像体的潜力,为再生医学应用创造了增强的BM移植.
- 跨物种嵌合体技术有望在未来开发具有改善肺组织再生能力的BM移植.
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