2. Academic Validation
  3. Medium from human iPSC-derived primitive macrophages promotes adult cardiomyocyte proliferation and cardiac regeneration

Medium from human iPSC-derived primitive macrophages promotes adult cardiomyocyte proliferation and cardiac regeneration

  • Nat Commun. 2025 Mar 27;16(1):3012. doi: 10.1038/s41467-025-58301-8.
Yi Xiao # 1 2 3,  Hao Zhang # 1 2 3,  Xu Liu 1 2 3,  Pengfei Xu 1 2 3,  Heng Du 1 2 3,  Jiawan Wang 4,  Jianghua Shen 1 2 3,  Yujing Li 1 2 3,  Yuhan Wang 1 2 3,  Chuting He 1 2 3,  Haiping Feng 1 2 3,  Jingfang Liu 5,  Yanan Zhou 1 2 3,  Siqi Liu 1 2 3,  Zeyu Gao 1 2,  Jingyi Zang 1 2,  Jinmiao Bi 1 2 3,  Tie-Shan Tang 1 2 3,  Qi Gu 1 2 3,  Tuo Wei 1 2 3,  Jun Wang 3 6,  Moshi Song 7 8 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 2 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
  • 3 University of Chinese Academy of Sciences, Beijing, China.
  • 4 Beijing Chao-Yang Hospital, Department of Anesthesiology, Beijing, China.
  • 5 Institutional Center for Shared Technologies and Facilities of Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • 6 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Chinese Academy of Sciences, Beijing, China.
  • 7 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. songmoshi@ioz.ac.cn.
  • 8 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. songmoshi@ioz.ac.cn.
  • 9 University of Chinese Academy of Sciences, Beijing, China. songmoshi@ioz.ac.cn.
  • # Contributed equally.
PMID: 40148355 DOI: 10.1038/s41467-025-58301-8
Abstract

Heart injury has been characterized by the irreversible loss of cardiomyocytes comprising the contractile tissues of the heart and thus strategies enabling adult cardiomyocyte proliferation are highly desired for treating various heart diseases. Here, we test the ability of human induced pluripotent stem cell-derived primitive macrophages (hiPMs) and their conditioned medium (hiPM-cm) to promote human cardiomyocyte proliferation and enhance cardiac regeneration in adult mice. We find that hiPMs promote human cardiomyocyte proliferation, which is recapitulated by hiPM-cm through the activation of multiple pro-proliferative pathways, and a secreted proteome analysis identifies five proteins participating in this activation. Subsequent in vivo experiments show that hiPM-cm promotes adult cardiomyocyte proliferation in mice. Lastly, hiPM-cm enhances cardiac regeneration and improves contractile function in injured adult mouse hearts. Together, our study demonstrates the efficacy of using hiPM-cm in promoting adult cardiomyocyte proliferation and cardiac regeneration to serve as an innovative treatment for heart disease.

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