Human amniotic MSCs-mediated anti-inflammation of CD206hiIL-10hi macrophages alleviates isoproterenol-induced ventricular remodeling in mice

• Published in: International immunopharmacology 2024-03, Vol.129, p.111660-111660, Article 111660
• Main Authors: Huang, Qi-Ming, Long, Ying-Lin, Wang, Jia-Nan, Wu, Jie, Tang, Wen-Long, Wang, Xiao-Yu, Zhang, Zhou-Hang, Zhuo, You-Qiong, Guan, Xiao-Hui, Deng, Ke-Yu, Xin, Hong-Bo
• Format: Article
• Language: English
• Subjects: Cardiac fibrosis; Human amniotic mesenchymal stem cells; Inflammation; Macrophages; Ventricular remodeling
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2024.111660

A mouse ventricular remodeling model including cardiac hypertrophy and fibrosis was generated by peritoneal injection of isoproterenol. hAMSCs significantly alleviated ISO-induced VR in mice and the underlying mechanism may be related to inhibition of the inflammation and fibrosis in hearts through promoting the polarization and infiltration of CD206high-IL10high macrophages in mice. [Display omitted] •Therapeutic effects and the underlying mechanism of hAMSCs in ISO-induced ventricular remodeling in mice. Human amniotic mesenchymal stem cells (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammation which makes them suitable for the treatment of various diseases. This study aimed to explore the therapeutic effect and molecular mechanism of hAMSCs in ventricular remodeling (VR). hAMSCs were characterized by a series of experiments such as flow cytometric analysis, immunofluorescence, differentiative induction and tumorigenicity. Mouse VR model was induced by isoproterenol (ISO) peritoneally, and the therapeutic effects and the potential mechanisms of hAMSCs transplantation were evaluated by echocardiography, carboxy fluorescein diacetate succinimidyl ester (CFSE) labeled cell tracing, histochemistry, qRT-PCR and western blot analysis. The co-culturing experiments were carried out for further exploring the mechanisms of hAMSCs-derived conditioned medium (CM) on macrophage polarization and fibroblast fibrosis in vitro. hAMSCs transplantation significantly alleviated ISO-induced VR including cardiac hypertrophy and fibrosis with the improvements of cardiac functions. CFSE labeled hAMSCs kept an undifferentiated state in heart, indicating that hAMSCs-mediated the improvement of ISO-induced VR might be related to their paracrine effects. hAMSCs markedly inhibited ISO-induced inflammation and fibrosis, seen as the increase of M2 macrophage infiltration and the expressions of CD206 and IL-10, and the decreases of CD86, iNOS, COL3 and αSMA expressions in heart, suggesting that hAMSCs transplantation promoted the polarization of M2 macrophages and inhibited the polarization of M1 macrophages. Mechanically, hAMSCs-derived CM significantly increased the expressions of CD206, IL-10, Arg-1 and reduced the expressions of iNOS and IL-6 in RAW264.7 macrophages in vitro. Interestingly, RAW264.7-CM remarkably promoted the expressions of anti-inflammatory factors such as IL-10, IDO, and COX2 in hAMSCs. Furthermore, th