Nature Communications (Apr 2023)

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

DOI
https://doi.org/10.1038/s41467-023-37954-3
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 16

Abstract

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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.