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

Tao Li
2015 Studies on Stem Cells Research and Therapy  
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
more » ... ed 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. unmet need to develop more effective, but less toxic treatments. In the last decade, hematopoietic stem cell transplantation (HSCT) has been reported as a promising therapy to achieve treatment-free, long-term remission in lupus [13], but the rates of relapse and treatment related toxicity are high, as are the rates of the development of a secondary autoimmune disorder [14] . On the other hand, mesenchymal stem cells (MSCs) are widely studied as an alternative cell source for their ability to differentiate into multiple mesenchymal lineages, including adipocytes, osteoblasts, chondrocytes, myocytes and tenocytes [15] [16] [17] . An important function of MSCs for autoimmune diseases is their broad immunomodulatory effect on various activated lymphoid cells, such as T cells, B cells, natural killer cells, and dendritic cells [18] [19] [20] . Therapeutic MSCs can be isolated from various tissues, including placenta, bone marrow, amniotic fluid, muscle, tooth, adipose tissue and umbilical cord blood. Recently, studies have focused on the use of human umbilical cord-derived MSCs (hUCMSCs). As an alternative to MSCs, hUCMSCs possess clear advantages, including easy production from a readily available source, low immunogenic potency, and high proliferative activity [21, 22] . Several studies have reported the therapeutic effect of hUCMSCs in bone regeneration, liver cirrhosis and acute liver failure models [23] [24] [25] . In addition, hUCMSCs have been shown to have immunosuppressive properties in reducing
doi:10.17352/sscrt.000003 fatcat:t5o477s5drbplkmn6qfzzhozd4