评估播种密度对心脏器官健康和功能对毒性研究的影响
Anirudha Harihara1, Khashayar Moshksayan1, Nima Momtahan2
1Department of Mechanical Engineering, The University of Texas at Austin, Austin, Texas, USA.
Tissue engineering. Part A
|November 3, 2025
概括
优化人类诱导的多能干细胞衍生心脏器官,20,000个细胞和7天培养增强心脏成熟度和药物诱导心脏毒性评估. 这种改进的模型显示对多克索鲁比辛毒性的敏感性更大.
科学领域:
- 干细胞生物学 干细胞生物学
- 心血管研究的心血管研究.
- 药物发现和毒理学
背景情况:
- 人类诱导的多能干细胞衍生心脏器官对于研究心脏生理学和药物毒性至关重要.
- 最佳的培养条件,特别是非心肌细胞和播种密度的作用,对于自我聚合的心脏有机体仍然不清楚.
研究的目的:
- 确定人类诱导多能干细胞衍生心脏器官的最佳播种密度,以改善心脏成熟度和药物毒性评估.
- 评估播种密度对有机体形态,基因表达,功能,活力和代谢活动随时间推移的影响.
主要方法:
- 用人类诱导的多能干细胞在不同种植密度 (例如20,000和80,000个细胞) 中生成心脏器官.
- 器官被评估为形态,基因表达,跳动功能,细胞活力 (细胞亡) 和线粒体活动.
- 模型对多克索鲁比诱导的心脏毒性的敏感性与2D培养相比较.
主要成果:
- 有机体大小稳定7天,无论种植密度如何.
- 用2万个细胞播种的器官体表现出增强的心脏特征,成熟度和减少纤维化,随着最小的亡和7天后更高的代谢活性.
- 与2D培养物相比,20,000个细胞的有机体模型显示出十倍以上的选择性指数,以及对多克索鲁比诱导的心脏毒性的提高敏感性.
结论:
- 在20,000个细胞的播种和7天的培养中,产生了具有最佳形态,转录特征,活力和跳动动力学的心脏器官.
- 这种优化的有机体模型为评估药物诱导心脏毒性提供了更敏感,更准确的平台,反映了比2D培养更好的体内条件.
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