Mesenchymal stem cells transfected with anti-miRNA-204-3p inhibit acute rejection after heart transplantation by targeting C-X-C motif chemokine receptor 4 (CXCR4) in vitro

Journal of Thoracic Disease

article

Lei Tuo¹  Hao Song³  Detian Jiang³  Xiao Bai³  Guangmin Song³ 

[1] Department of Cardiovascular Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University;Department of Cardiovascular Surgery, Weifang Yidu Central Hospital;Department of Cardiovascular Surgery, Qilu Hospital of Shandong University

关键词: Heart transplantation (HTx);    acute rejection (AR);    mesenchymal stem cell (MSC);    miRNA-204-3p;    macrophage polarization;   

DOI  :  10.21037/jtd-21-1293

学科分类：呼吸医学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

Background: Mesenchymal stem cells (MSCs) are a promising treatment for acute rejection (AR) after heart transplantation (HTx) owing to their immunomodulatory functions by promoting the transformation of macrophages from the M0 to M2 phenotype. However, it is undetermined whether surface expression of C-X-C motif chemokine receptor 4 (CXCR4) by MSCs influences macrophage polarization. In this study, we investigated the effects of MSCs on macrophages caused by CXCR4, and detected the underlying mechanism, which may contribute to improving HTx outcomes. Methods: The MSCs were extracted from rat bone marrow and identified using flow cytometry. We subsequently observed the effects of CXCR4 and anti-miRNA-204-3p on cell proliferation and migration, and the effects on macrophage polarization. Dual luciferase reporter assay was used to explore whether miRNA-204-3p was an upstream microRNA (miRNA) of CXCR4. A series of rescue experiments were performed to further confirm the inhibitory effect of miRNA-204-3p on CXCR4. Results: The results showed that CXCR4 could promote the proliferation and migration of MSCs. Furthermore, it facilitated MSC-mediated macrophage transformation from the M0 to M2 phenotype. In addition, miRNA-204-3p inhibited the function of CXCR4 of MSCs. Conclusions: Regulated by miRNA-204-3p, CXCR4 could inhibit the progression of AR after HTx. This study provides a new insight of the treatment of AR after HTx.

【 授权许可】

Unknown