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 () and Yingdai Gao ()
Additional contact information
Yinghui Li: Chinese Academy of Medical Sciences & Peking Union Medical College
Mei He: Chinese Academy of Medical Sciences & Peking Union Medical College
Wenshan Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Wei Liu: Tsinghua University
Hui Xu: Chinese Academy of Medical Sciences & Peking Union Medical College
Ming Yang: Chinese Academy of Medical Sciences & Peking Union Medical College
Hexiao Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Haiwei Liang: Tsinghua University
Wenjing Li: Tsinghua University
Zhaozhao Wu: Tsinghua University
Weichao Fu: Chinese Academy of Medical Sciences & Peking Union Medical College
Shiqi Xu: Chinese Academy of Medical Sciences & Peking Union Medical College
Xiaolei Liu: Chinese Academy of Medical Sciences & Peking Union Medical College
Sibin Fan: Chinese Academy of Medical Sciences & Peking Union Medical College
Liwei Zhou: Chinese Academy of Medical Sciences & Peking Union Medical College
Chaoqun Wang: Chinese Academy of Medical Sciences & Peking Union Medical College
Lele Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Yafang Li: Chinese Academy of Medical Sciences & Peking Union Medical College
Jiali Gu: Chinese Academy of Medical Sciences & Peking Union Medical College
Jingjing Yin: Chinese Academy of Medical Sciences & Peking Union Medical College
Yiran Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Yonghui Xia: Chinese Academy of Medical Sciences & Peking Union Medical College
Xuemei Mao: Tianjin Hospital of Integrated Traditional Chinese and Western Medicine
Tao Cheng: Chinese Academy of Medical Sciences & Peking Union Medical College
Jun Shi: Chinese Academy of Medical Sciences & Peking Union Medical College
Yanan Du: Tsinghua University
Yingdai Gao: Chinese Academy of Medical Sciences & Peking Union Medical College

Nature Communications, 2023, vol. 14, issue 1, 1-16

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 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.

Date: 2023
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DOI: 10.1038/s41467-023-37954-3

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