Medium from human iPSC-derived primitive macrophages promotes adult cardiomyocyte proliferation and cardiac regeneration
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.
Authors
- Jianghua Shen (ORCID: https://orcid.org/0000-0002-4606-542X)
- Jiawan Wang (ORCID: https://orcid.org/0000-0002-2199-0483)
- Yanan Zhou (ORCID: https://orcid.org/0000-0002-4880-6439)
- Moshi Song (ORCID: https://orcid.org/0000-0001-9929-8975)
- Yi Xiao (ORCID: https://orcid.org/0000-0003-1603-8946)
- Chuting He
- Zeyu Gao (ORCID: https://orcid.org/0000-0002-3594-8366)
- Jingfang Liu (ORCID: https://orcid.org/0000-0002-6845-1268)
- Pengfei Xu (ORCID: https://orcid.org/0000-0002-0389-1182)
- Heng Du (ORCID: https://orcid.org/0009-0006-1950-9650)
- Qi Gu (ORCID: https://orcid.org/0000-0001-9387-9525)
- Tie-Shan Tang (ORCID: https://orcid.org/0000-0001-8975-6338)
- Haiping Feng
- Xu Liu (ORCID: https://orcid.org/0000-0003-1970-0608)
- Yuhan Wang (ORCID: https://orcid.org/0009-0006-8868-5316)
- Jun Wang (ORCID: https://orcid.org/0000-0002-8859-7707)
- Siqi Liu (ORCID: https://orcid.org/0000-0001-9744-3681)
- Hao Zhang (ORCID: https://orcid.org/0000-0001-9474-3195)
- Yujing Li (ORCID: https://orcid.org/0000-0002-4363-2484)
- Jinmiao Bi (ORCID: https://orcid.org/0000-0003-1366-5469)
- Tuo Wei (ORCID: https://orcid.org/0000-0002-2823-9721)
- Jian Zang (ORCID: https://orcid.org/0009-0001-1251-977X)
Institutions
- Chinese Academy of Sciences (CN)
- Beijing Chao-Yang Hospital, Capital Medical University (CN)
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Institute of Microbiology (CN)
- University of Chinese Academy of Sciences (CN)
- Institute of Zoology (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-27
- DOI
- https://doi.org/10.1038/s41467-025-58301-8
- Citations
- 11
- Primary Topic
- Tissue Engineering and Regenerative Medicine
- Type
- article
- Field-Weighted Citation Impact
- 22.07