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干细胞的挑战和机遇

Kenta Ite¹, Masashi Toyoda², Saeko Akiyama³

¹Center for Regenerative Medicine, National Center for Child Health and Development Research Institute, Tokyo, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Progress in molecular biology and translational science

|September 7, 2023

概括

肝脏中的殖民地形成单元 (CFU-L) 可以可靠地测量肝细胞干和移植. 这种新的测定方法为评估肝脏干细胞功能提供了一种定量方法,与目前用于肝细胞样细胞的方法不同.

科学领域:

肝病学肝病学是一种肝病学.
干细胞生物学干细胞生物学
再生医学是一种再生医学.

背景情况:

来自人类多能干细胞 (PSC) 的肝细胞样细胞 (HLC) 是有前途的,但体内移植和功能不佳.
目前的差异化协议还没有克服肝损伤模型中HLCs的植入限制.
器官衍生的肝细胞在体内表现出可再生的殖民地形成,与HLC不同.

研究的目的:

提出和验证一种新的定量测试,用于评估肝细胞干性,移植和功能.
引入"肝脏中的殖民地形成单位" (CFU-L) 概念作为可靠的指标.
建立CFU-L作为类似于造血干细胞"中的殖民地形成单位" (CFU-s) 的测量标准.

主要方法:

在小鼠肝损伤模型中,HLCs和器官衍生肝细胞之间的体内移植和殖民地形成的比较.
假设CFU-L作为一种基于观察到的殖民地形成的功能干度测试.
利用单细胞起源证据 (统一的基因失活) 来支持CFU-L作为定量衡量.

主要成果:

肝细胞样细胞未能在小鼠肝损伤模型中植入.
器官衍生的肝细胞在相同的模型中始终形成殖民地.
建议CFU-L的概念作为直接衡量体内移植和增殖肝细胞的直接测量.

结论:

肝脏中的殖民地形成单位 (CFU-L) 代表了量化肝细胞干细胞和体内移植潜力的强有力的测试方法.
CFU-L提供了一种标准化的方法来评估肝细胞的功能能力,这对于基于细胞的疗法至关重要.
这种方法为肝脏研究中的干细胞评估提供了一个新的范式,反映了血液形成中的既定方法.

关键词:

类似肝细胞的细胞.奇默的老鼠奇默的老鼠奇默的老鼠在脏中的殖民地形成单位.药物诱导的肝损伤是药物诱导的额外骨髓性红色素质形成.造血干细胞造血干细胞肝脏干细胞是肝脏的干细胞.人类多能干细胞干细胞

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