Therapeutic Effects of Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation in Experimental Lupus Nephritis

Abstract

Mesenchymal stem cells (MSCs) have been shown to possess immunomodulatory properties. Systemic lupus erythematosus is an autoimmune disease that results in nephritis and subsequent destruction of renal microstructure. We investigated whether transplantation of human umbilical cord blood-derived MSCs (uMSCs) is useful in alleviating lupus nephritis in a murine model. It was found that uMSCs transplantation significantly delayed the development of proteinuria, decreased anti-dsDNA, alleviated renal injury, and prolonged the life span. There was a trend of decreasing T-helper (Th) 1 cytokines (IFN-γ, IL-2) and proinflammatory cytokines (TNF-α, IL-6, IL-12) and increasing Th2 cytokines (IL-4, IL-10). The in vitro coculture experiments showed that uMSCs only inhibited lymphocytes and splenocytes proliferation but not mesangial cells. Long-term engraftment of uMSCs in the kidney was not observed either. Together, these findings indicated that uMSCs were effective in decreasing renal inflammation and alleviating experimental lupus nephritis by inhibiting lymphocytes, inducing polarization of Th2 cytokines, and inhibition of proinflammatory cytokines production rather than direct engraftment and differentiating into renal tissue. Therapeutic effects demonstrated in this preclinical study support further exploration of the possibility to use uMSCs from mismatched donors in lupus nephritis treatment.

Prostaglandin E2 Potentiates Mesenchymal Stem Cell–Induced IL-10+IFN-γ+CD4+ Regulatory T Cells To Control Transplant Arteriosclerosis

“…Mesenchymal stem cells (MSCs), which modulate various aspects of innate and adaptive immunity, have been applied to the treatment of autoimmune diseases (3,4), allergic airway inflammation (5), and allograft rejection (6)(7)(8). In adaptive immunity, MSCs tilt T cell responses toward regulatory T cell (Treg) profiles both in vitro (9-13) and in vivo.…”

Mesenchymal Stem Cells Prevent Hydrocephalus After Severe Intraventricular Hemorrhage

“…14,15,17 Although the anti-inflammatory action of MSCs has been reported in various disorders, including BPD, 14,15 acute respiratory distress syndrome, 16 and neonatal stroke, 17 the mechanism remains to be delineated. Anti-inflammatory effects of MSC transplantation might include immune modulation 36 and delivery of various growth factors and cytokines, such as vascular endothelial growth factor, hepatocyte growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and IL-10. 13,[37][38][39] By secreting these trophic factors, MSCs might promote a shift from a proinflammatory environment toward an anti-inflammatory or tolerant environment.…”

A big step forward in the treatment of refractory systemic lupus erythematosus: allogenic mesenchymal stem cell transplantation

“…The efficacy of SCT in SLE has been attributed to resetting an aberrant immune system either through direct immune replacement with hematopoietic stem cells or through immunomodulation with mesenchymal stem cells (MSCs), shifting the immune system from a highly pro-inflammatory disease environment to a less inflammatory one [3] . Unlike hematopoietic stem cells, MSCs are multipotent cells capable of differentiating into a variety of mesenchymal lineages including cartilage, bone, muscle, tendon, ligament and adipose tissue, and lack significant immunogenicity for no MHC-II and costimulatory molecule expression.…”