2. Academic Validation
  3. Progenitor effect in the spleen drives early recovery via universal hematopoietic cell inflation

Progenitor effect in the spleen drives early recovery via universal hematopoietic cell inflation

  • Cell Rep. 2025 Feb 25;44(2):115241. doi: 10.1016/j.celrep.2025.115241.
Takao Yogo 1,  Hans Jiro Becker 2,  Takaharu Kimura 2,  Satoshi Iwano 3,  Takahiro Kuchimaru 4,  Atsushi Miyawaki 5,  Tomomasa Yokomizo 6,  Toshio Suda 7,  Atsushi Iwama 8,  Satoshi Yamazaki 9
Affiliations

Affiliations

  • 1 Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Division of Cell Engineering, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Electronic address: takayogo0430@g.ecc.u-tokyo.ac.jp.
  • 2 Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Division of Cell Engineering, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • 3 Institute for Tenure Track Promotion, University of Miyazaki, Miyazaki, Japan.
  • 4 Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan.
  • 5 Laboratory for Cell Function Dynamics, RIKEN Center for Brain Science, RIKEN, Saitama, Japan.
  • 6 Department of Microscopic and Developmental Anatomy, Tokyo Women's Medical University, Tokyo, Japan.
  • 7 International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan; Stem Cell Biology Institute of Hematology, Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 8 Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • 9 Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Division of Cell Engineering, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Laboratory for Stem Cell Therapy, Faculty of Medicine, Tsukuba University, Ibaraki, Japan. Electronic address: y-sato4@g.ecc.u-tokyo.ac.jp.
PMID: 39864058 DOI: 10.1016/j.celrep.2025.115241
Abstract

Hematopoietic stem cells (HSCs) possess the capacity to regenerate the entire hematopoietic system. However, the precise HSC dynamics in the early post-transplantation phase remain an enigma. Clinically, the initial hematopoiesis in the post-transplantation period is critical, necessitating strategies to accelerate hematopoietic recovery. Here, we uncovered the spatiotemporal dynamics of early active hematopoiesis, "hematopoietic cell inflation," using a highly sensitive in vivo imaging system. Hematopoietic cell inflation occurs in three peaks in the spleen after transplantation, with common myeloid progenitors (CMPs), notably characterized by HSC-like signatures, playing a central role. Leveraging these findings, we developed expanded CMPs (exCMPs), which exhibit a gene expression pattern that selectively proliferates in the spleen and promotes hematopoietic expansion. Moreover, universal exCMPs supported early hematopoiesis in allogeneic transplantation. Human universal exCMPs have the potential to be a viable therapeutic enhancement for all HSC transplant patients.

Keywords

CP: Stem cell research; cell therapy; hematopoietic cell inflation; hematopoietic stem cell; spatiotemporal dynamics; universal common myeloid progenitor.

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