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.
Keywords: Heart transplantation (HTx); acute rejection (AR); macrophage polarization; mesenchymal stem cell (MSC); miRNA-204-3p.
2021 Journal of Thoracic Disease. All rights reserved.