脂肪组织衍生中酶体干细胞延长寿命,增强肝细胞器官中的肝功能
Sun A Ock1, Seo-Yeon Kim1, Won Seok Ju1
1Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, 1500 Kongjwipatjwi-ro, Iseo-myeon, Wanju-gun 55365, Republic of Korea.
International journal of molecular sciences
|October 28, 2023
概括
研究人员通过与脂肪组织衍生的介质干细胞 (A-MSCs) 共同培养,改善了肝细胞器官 (HOs). 这增强了肝功能并将寿命延长到126天,为毒性测试和营养评估创造了更好的模型.
科学领域:
- * * 干细胞生物学
- * 有机物技术 * 有机物技术
- * 肝病学 肝病学是一门专业.
背景情况:
- * 3D培养中的初级肝细胞 (PHs) 在体外寿命有限.
- * 现有的肝细胞有机体类型在寿命和功能方面面临挑战.
- * 需要改善肝脏研究的体外模型.
研究的目的:
- *使用原发性肝细胞 (PHs) 生产长寿命和功能性肝细胞器官 (HOs).
- * 调查与脂肪组织衍生的介质干细胞 (A-MSCs) 共同培养对HO寿命和功能的影响.
- * 评估这些增强型HO的毒性测试和营养评估潜力.
主要方法:
- * 在3D Matrigel 圆顶培养中从冷解的 PH 产生 HO.
- * 在3D Matrigel 圆顶系统中与A-MSC共同培养HO.
- *对HO寿命,肝功能标志物 (白蛋白,尿素,葡萄糖) 和随着时间推移的基因表达的评估.
主要成果:
- *与A-MSC共同培养增加了HO寿命的3.5倍,达到126天.
- * 观察到肝功能改善,包括白蛋白和尿素分泌量增加以及葡萄糖消耗.
- *在HO中鉴定了胆细胞标记物 (CK19,EPCAM);在100天后观察到TP53-P21,EPCAM,ALB和CYP3A29表达的变化.
结论:
- * 同培养PH衍生HO与A-MSC显著改善体外寿命和肝功能.
- *这些增强的HOO作为大规模人类肝毒性测试的宝贵平台.
- * 改进的HOS可以作为精确的工具用于牲畜营养评估.
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