2. Academic Validation
  3. Intramyocardial injected human umbilical cord-derived mesenchymal stem cells (HucMSCs) contribute to the recovery of cardiac function and the migration of CD4+ T cells into the infarcted heart via CCL5/CCR5 signaling

Intramyocardial injected human umbilical cord-derived mesenchymal stem cells (HucMSCs) contribute to the recovery of cardiac function and the migration of CD4+ T cells into the infarcted heart via CCL5/CCR5 signaling

  • Stem Cell Res Ther. 2022 Jun 11;13(1):247. doi: 10.1186/s13287-022-02914-z.
Jing Liu  # 1 2,  Xiaoting Liang  # 1 3,  Mimi Li 1 4,  Fang Lin 1 4,  Xiaoxue Ma 1 4,  Yuanfeng Xin 1 5,  Qingshu Meng 1 4,  Rulin Zhuang 1 5,  Qingliu Zhang 6 7,  Wei Han 6 7,  Ling Gao 8,  Zhiying He 3 7 9,  Xiaohui Zhou 10 11,  Zhongmin Liu 12 13 14 15
Affiliations

Affiliations

  • 1 Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China.
  • 2 Department of Burn and Plastic Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
  • 3 Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, People's Republic of China.
  • 4 Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China.
  • 5 Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China.
  • 6 Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China.
  • 7 Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, 200120, People's Republic of China.
  • 8 Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China.
  • 9 Shanghai Engineering Research Center of Stem Cells Translational Medicine, Shanghai, 200335, People's Republic of China.
  • 10 Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China. [email protected].
  • 11 Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China. [email protected].
  • 12 Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China. [email protected].
  • 13 Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People's Republic of China. [email protected].
  • 14 Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong, Shanghai, 200120, People's Republic of China. [email protected].
  • 15 Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, 200120, People's Republic of China. [email protected].
  • # Contributed equally.
PMID: 35690805 DOI: 10.1186/s13287-022-02914-z
Abstract

Background: Human umbilical cord-derived mesenchymal stem cells (HucMSCs) have been recognized as a promising cell for treating myocardial infarction (MI). Inflammatory response post MI is critical in determining the cardiac function and subsequent adverse left ventricular remodeling. However, the local inflammatory effect of HucMSCs after intramyocardial injection in murine remains unclear.

Methods: HucMSCs were cultured and transplanted into the mice after MI surgery. Cardiac function of mice were analyzed among MI-N.S, MI-HucMSC and MI-HucMSC-C-C Motif Chemokine Receptor 5 (CCR5) antagonist groups, and angiogenesis, fibrosis and hypertrophy, and immune cells infiltration of murine hearts were evaluated between MI-N.S and MI-HucMSC groups. We detected the expression of inflammatory cytokines and their effects on CD4+ T cells migration.

Results: HucMSCs treatment can significantly improve the cardiac function and some cells can survive at least 28 days after MI. Intramyocardial administration of HucMSCs also improved angiogenesis and alleviated cardiac fibrosis and hypertrophy. Moreover, we found the much higher numbers of CD4+ T cells and CD4+FoxP3+ regulatory T cells (Tregs) in the heart with HucMSCs than that with N.S treatment on day 7 post MI. In addition, the protein level of C-C Motif Chemokine Ligand 5 (CCL5) greatly increased in HucMSCs treated heart compared to MI-N.S group. In vitro, HucMSCs inhibited CD4+ T cells migration and addition of CCL5 antibody or CCR5 Antagonist significantly reversed this effect. In vivo results further showed that addition of CCR5 Antagonist can reduce the cardioprotective effect of HucMSCs administration on day 7 post MI injury.

Conclusion: These findings indicated that HucMSCs contributed to cardiac functional recovery and attenuated cardiac remodeling post MI. Intramyocardial injection of HucMSCs upregulated the CD4+FoxP3+ Tregs and contributed to the migration of CD4+ T cells into the injured heart via CCL5/CCR5 pathway.

Keywords

CCL5/CCR5; CD4+ T cells; Human umbilical cord-derived mesenchymal stem cells; Intramyocardial injection; Myocardial infarction.

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