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- Title
Expansion of human megakaryocyte-biased hematopoietic stem cells by biomimetic Microniche.
- Authors
Li, Yinghui; He, Mei; Zhang, Wenshan; Liu, Wei; Xu, Hui; Yang, Ming; Zhang, Hexiao; Liang, Haiwei; Li, Wenjing; Wu, Zhaozhao; Fu, Weichao; Xu, Shiqi; Liu, Xiaolei; Fan, Sibin; Zhou, Liwei; Wang, Chaoqun; Zhang, Lele; Li, Yafang; Gu, Jiali; Yin, Jingjing
- 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 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. An effective expansion system for therapeutic megakaryocyte-biased hematopoietic stem cells has not been developed. Here the authors present a microniche-based system that supports scalable expansion of human Mk-biased HSCs and identify their immune phenotype.
- Subjects
HEMATOPOIETIC stem cells; HUMAN beings
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-37954-3