Transplantation of umbilical cord mesenchymal stem cells alleviates lupus nephritis in MRL/lpr mice

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, which, despite the advances in immunosuppressive medical therapies, remains potentially fatal in some patients, especially in treatment-refractory patients. This study found that transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) has the same therapeutic effect as transplantation of bone marrow mesenchymal stem cells (BM-MSCs), which has been reported to be efficient in treating SLE-related symptoms in MRL/lpr mice. Multi-treatment (at the 18th, 19th, and 20th weeks of age) of 1 × 10⁶ UC-MSCs was able to decrease the levels of 24-h proteinuria, serum creatinine, and anti-double-stranded DNA (dsDNA) antibody, and the extent of renal injury such as crescent formation in MRL/lpr mice. A lower, but still significant, reduction in these parameters was also observed in mice receiving a single dose of UC-MSCs (at the 18th week). UC-MSCs treatment also inhibited expression of monocyte chemotactic protein-1 (MCP-1) and high-mobility group box 1 (HMGB-1) expression in a similar fashion. UC-MSCs labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) were found in the lungs and kidneys 1 week post infusion. In addition, after 11 weeks post UC-MSCs infusion, human cells were found in kidney of UC-MSCs-treated mice. These findings indicated that UC-MSCs transplantation might be a potentially promising approach in the treatment of lupus nephritis, possibly by inhibiting MCP-1 and HMGB-1 production. Lupus (2010) 19, 1502—1514.

Keywords

high-mobility group box 1 lupus nephritis monocyte chemotactic protein-1 regulatory T cell systemic lupus erythematosus umbilical cord mesenchymal stem cell

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