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Expansion of human megakaryocyte-biased hematopoietic stem cells by biomimetic Microniche

Author

Listed:
  • Yinghui Li

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Mei He

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Wenshan Zhang

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Wei Liu

    (Tsinghua University
    Beijing CytoNiche Biotechnology Co. Ltd.)

  • Hui Xu

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Ming Yang

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Hexiao Zhang

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Haiwei Liang

    (Tsinghua University)

  • Wenjing Li

    (Tsinghua University)

  • Zhaozhao Wu

    (Tsinghua University)

  • Weichao Fu

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Shiqi Xu

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Xiaolei Liu

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Sibin Fan

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Liwei Zhou

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Chaoqun Wang

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Lele Zhang

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Yafang Li

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Jiali Gu

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Jingjing Yin

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Yiran Zhang

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Yonghui Xia

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Xuemei Mao

    (Tianjin Hospital of Integrated Traditional Chinese and Western Medicine)

  • Tao Cheng

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Jun Shi

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

  • Yanan Du

    (Tsinghua University
    Beijing CytoNiche Biotechnology Co. Ltd.)

  • Yingdai Gao

    (Chinese Academy of Medical Sciences & Peking Union Medical College
    Tianjin Institutes of Health Science)

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.

Suggested Citation

  • 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 Wan, 2023. "Expansion of human megakaryocyte-biased hematopoietic stem cells by biomimetic Microniche," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37954-3
    DOI: 10.1038/s41467-023-37954-3
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