1区 · 综合性期刊
ArticleOA
作者: Li, Yafang ; Zhang, Yiran ; Liu, Xiaolei ; Gao, Yingdai ; Zhang, Wenshan ; Wu, Zhaozhao ; He, Mei ; Zhang, Hexiao ; Liang, Haiwei ; Xia, Yonghui ; Li, Wenjing ; Yang, Ming ; Zhang, Lele ; Mao, Xuemei ; Liu, Wei ; Xu, Shiqi ; Cheng, Tao ; Gu, Jiali ; Li, Yinghui ; Xu, Hui ; Shi, Jun ; Wang, Chaoqun ; Fu, Weichao ; Du, Yanan ; Fan, Sibin ; Yin, Jingjing ; Zhou, Liwei
Limited numbers of available hematopoietic stem cells (HSCs) limit the widespread use of HSC-based therapies. Expansion systems for functional heterogenous HSCs remain to be optimized. Here, we present a convenient strategy for human HSC expansion based on a biomimetic Microniche. After demonstrating the expansion of HSC from different sources, we find that our Microniche-based system expands the therapeutically attractive megakaryocyte-biased HSC. We demonstrate scalable HSC expansion by applying this strategy in a stirred bioreactor. Moreover, we identify that the functional human megakaryocyte-biased HSCs are enriched in the CD34+CD38-CD45RA-CD90+CD49f lowCD62L-CD133+ subpopulation. Specifically, the expansion of megakaryocyte-biased HSCs is supported by a biomimetic niche-like microenvironment, which generates a suitable cytokine milieu and supplies the appropriate physical scaffolding. Thus, beyond clarifying the existence and immuno-phenotype of human megakaryocyte-biased HSC, our study demonstrates a flexible human HSC expansion strategy that could help realize the strong clinical promise of HSC-based therapies.