Expansion of human megakaryocyte-biased hematopoietic stem cells by biomimetic Microniche
Yinghui Li, Mei He, Wenshan Zhang, Wei Liu, Hui Xu, Ming Yang, Hexiao Zhang, Haiwei Liang, Wenjing Li, Zhaozhao Wu, Weichao Fu, Shiqi Xu, Xiaolei Liu, Sibin Fan, Liwei Zhou, Chaoqun Wang, Lele Zhang, Yafang Li, Jiali Gu, Jingjing Yin, Yiran Zhang, Yonghui Xia, Xuemei Mao, Tao Cheng, Jun Shi, Yanan Du, Yingdai Gao
Abstract
Abstract 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 low CD62L - 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.