Li Xuejia, Xia Chengxiang, Wang Tongjie, Liu Lijuan, Zhao Qianhao, Yang Dan, Hu Fangxiao, Zhang Mengyun, Huang Ke, Geng Yang, Zheng Yi, Guan Yuxian, Wu Hongling, Chen Xiaoli, Pan Guangjin, Chen Jiekai, Du Juan, Wang Jinyong
Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Stem Cell Res. 2017 May;21:32-39. doi: 10.1016/j.scr.2017.03.014. Epub 2017 Mar 21.
In the field of hematopoietic regeneration, deriving hematopoietic stem cells (HSCs) from pluripotent stem cells with engraftment potential is the central mission. Unstable hematopoietic differentiation protocol due to variation factors such as serums and feeder cells, remains a major technical issue impeding the screening of key factors for the derivation of HSCs. In combination with hematopoietic cytokines, UM171 has the capacity to facilitate the maintenance and expansion of human primary HSCs in vitro. Here, using a serum-free, feeder-free, and chemically defined induction protocol, we observed that UM171 enhanced hematopoietic derivation through the entire process of hematopoietic induction in vitro. UM171 facilitated generation of robust CD34CD45 derivatives that formed more and larger sized CFU-GM as well as larger sized CFU-Mix. In our protocol, the derived hematopoietic progenitors failed to engraft in NOG mice, indicating the absence of long-term HSC from these progenitors. In combination with other factors and protocols, UM171 might be broadly used for hematopoietic derivation from human pluripotent stem cells in vitro.
在造血再生领域，从具有植入潜力的多能干细胞中获取造血干细胞（HSCs）是核心任务。由于血清和饲养细胞等可变因素导致的造血分化方案不稳定，仍然是阻碍筛选HSCs衍生关键因子的主要技术问题。与造血细胞因子联合使用时，UM171具有促进人原代HSCs体外维持和扩增的能力。在此，我们采用无血清、无饲养细胞且化学成分明确的诱导方案，观察到UM171在体外造血诱导的整个过程中增强了造血衍生。UM171促进了强大的CD34CD45衍生物的生成，这些衍生物形成了越来越多且更大尺寸的CFU - GM以及更大尺寸的CFU - Mix。在我们的方案中，所衍生的造血祖细胞未能在NOG小鼠中植入，这表明这些祖细胞中不存在长期造血干细胞。与其他因子和方案联合使用时，UM171可能广泛用于体外从人多能干细胞进行造血衍生。
