2. Academic Validation
  3. Transient mechanical activation of the Piezo1 channel facilitates ex vivo expansion of hematopoietic stem cells

Transient mechanical activation of the Piezo1 channel facilitates ex vivo expansion of hematopoietic stem cells

  • Cell Res. 2026 Jan 9. doi: 10.1038/s41422-025-01209-1.
Qiwei Wang # 1 2,  Xin Zeng # 1 2,  Haoxiang Yang # 3 4,  Huan Lu # 1 2,  Lingli Jiang # 5,  Lizhen Xu 6,  Jinxin Li 1 2,  Jingyi Li 1 2,  Yingli Han 1 2,  Xiaoyan Wu 7,  Yuanhong Zhou 8,  Xiaolan Chen 9,  Yanmin Zhao 1 2,  Jimin Shi 1 2,  Yi Luo 1 2,  Fang Ni 4,  Jie Sun 1 2 7,  Qian Zhao 9,  Fan Yang 1 6,  Peng Xia 7,  Hongyuan Jiang 10 11,  He Huang 12 13,  Pengxu Qian 14 15
Affiliations

Affiliations

  • 1 Bone Marrow Transplantation Center of the First Affiliated Hospital and Center for Stem Cell and Regenerative Medicine & Liangzhu Laboratory, Zhejiang University School of Medicine, State Key Laboratory of Experimental Hematology, Hangzhou, Zhejiang, China.
  • 2 Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, China.
  • 3 Hefei National Laboratory for Physical Science at the Microscale, CAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of China, Hefei, Anhui, China.
  • 4 Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
  • 5 Basic Medical Research Center, School of Medicine, Nantong University, Nantong, Jiangsu, China.
  • 6 Department of Biophysics and Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 7 Department of Cell Biology and Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 8 Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China.
  • 9 State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, China.
  • 10 Hefei National Laboratory for Physical Science at the Microscale, CAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of China, Hefei, Anhui, China. [email protected].
  • 11 Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. [email protected].
  • 12 Bone Marrow Transplantation Center of the First Affiliated Hospital and Center for Stem Cell and Regenerative Medicine & Liangzhu Laboratory, Zhejiang University School of Medicine, State Key Laboratory of Experimental Hematology, Hangzhou, Zhejiang, China. [email protected].
  • 13 Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, China. [email protected].
  • 14 Bone Marrow Transplantation Center of the First Affiliated Hospital and Center for Stem Cell and Regenerative Medicine & Liangzhu Laboratory, Zhejiang University School of Medicine, State Key Laboratory of Experimental Hematology, Hangzhou, Zhejiang, China. [email protected].
  • 15 Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, China. [email protected].
  • # Contributed equally.
PMID: 41507440 DOI: 10.1038/s41422-025-01209-1
Abstract

Achieving long-term ex vivo expansion of functional hematopoietic stem cells (HSCs) is essential for advancing HSC-based clinical therapies. Although mechanosensitive ion channels are known to play key roles in the hematopoietic system, their involvement in HSC expansion remains unclear. Here, we show that Piezo1 is highly expressed in HSCs. Both genetic deletion and prolonged chemical activation of Piezo1 impair cultured HSC function, indicating that transient mechanical activation of Piezo1 is required for maintenance of HSCs in culture. To achieve this, we screened various microspheres and found that PS500 (500-nm polystyrene microspheres) significantly enhanced ex vivo expansion of mouse bone marrow HSCs with long-term repopulating capacity. PS500 also expanded human umbilical cord blood HSCs capable of engraftment in immunodeficient mice. Mechanistically, PS500 activates Piezo1, triggering CA2+-dependent expression of proliferative cytokines and subsequent STAT3 activation, which support HSC self-renewal and proliferation. Together, these findings show that PS500 enables transient Piezo1 activation and efficient, non-toxic expansion of functional HSCs, offering a promising approach for the generation of transplantable HSCs for clinical use.

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