Background Bone marrow–derived mesenchymal stem cells (BM-MSCs) are multipotent cells characterized by immunomodulatory properties and are therefore considered as a promising cell therapy for autoimmune diseases. It has been shown that BM-MSCs from healthy donors were able to inhibit the activation of B cells in vitro and in vivo. Our previous study revealed that BM-MSCs from patients with systemic lupus erythematosus (SLE) possessed some dysfunctions.
Objectives This study aimed to assess whether inhibition on B cell activation by BM-MSCs in MRL/lpr mice, an animal model of SLE, was impaired and the possible mechanisms involved in this process.
Methods BM-MSCs were isolated and expanded from either C57BL/6J or MRL/lpr mice. The effects of BM-MSCs on the proliferation and differentiation to plasma cells of normal splenic B cell isolated from C57BL/6J mice were evaluated in vitro. And the differential expression of CCL2 on BM-MSCs from C57BL/6J or MRL/lpr mice was detected. Lupus mice were treated with these two different BM-MSCs respectively, and the levels of serum auto-antibodies and immunoglobulin deposition in the kidney were monitored.
Results BM-MSCs from C57BL/6J mice inhibited the proliferation and differentiation to plasma cells of B cells in vitro. This inhibitory effect was mediated by soluble factors, including CCL2, as neutralizing CCL2 could abolish the suppressive effect on B cells mediated by normal BM-MSCs. Inhibition on B-cell proliferation and differentiation by BM-MSCs from MRL/lpr mice was impaired, partially resulted from down-regulated expression of CCL2. The addition of processed CCL2 restored inhibitory effects of BM-MSCs from MRL/lpr mice on B-cells. In vivo treatment with BM-MSCs from MRL/lpr mice did not reduce the levels of serum pathological antibody production and immunoglobulin deposition in the kidney compared with treatment with BM-MSCs from C57BL/6J mice.
Conclusions Our findings suggest that inhibitory effects of BM-MSCs on B-cell are mediated by soluble factors including CCL2. Impaired inhibition of BM-MSCs from MRL/lpr mice on B-cell maybe attributes to the down-regulation of CCL2 expression, which may play an important role in the pathogenesis of SLE.
Disclosure of Interest None Declared