Human Umbilical Cord Mesenchymal Stem Cells Suppress Systemic Lupus Erythematosus Lesions by Rebalancing CD4+/CD8+ Cell Population

Despite considerable advances in the treatment for systemic lupus erythematosus (SLE), there is still an unmet need to develop novel therapeutic approaches with improved efficacy and lower side effects. Here we explore human umbilical cord-derived mesenchymal stem cells (hUCMSCs) as a promising treatment for SLE induced by concanavalin A-activated spleno-lymphocyte in BALB/c mice. The isolated hUCMSCs, carrying specific MSC cell surface markers (CD105, CD73 and CD90), exhibited the potential to differentiate into osteogenic and adipogenic lineages. In mice with SLE, transplantation of hUCMSCs improved disease symptoms by decreasing the levels of serum autoantibody (anti-dsDNA and anti-nuclear) and cytokines (TNF-α and IFN-γ). The cell therapy significantly alleviated renal lesions by lowering serum urea nitrogen, creatine and uric acid, and increasing albumin. Using immunohistochemical staining, we found that that hUCMSCs decreased endocapillary hypercellularity, glomerular degeneration, and complement C3 immune complex deposition in the kidney. Mechanically, the therapy with hUCMSCs decreased CD4+/CD8+ cell ratio in animals. These data suggest that hUCMSCs may modulate autoimmunity in SLE mice by rebalancing CD4+/CD8+ cell population. Transplantation of hUCMSCs may be explored as a promising alternative approach in the treatment of human lupus.