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

Author:

Gu Z.1,Akiyama K.2,Ma X.3,Zhang H.3,Feng X.3,Yao G.3,Hou Y.4,Lu L.5,Gilkeson GS6,Silver RM6,Zeng X.7,Shi S.2,Sun L.8

Affiliation:

1. Department of Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, Department of Rheumatology, The Affiliated Hospital of Nantong University, Nantong, China

2. Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, USA

3. Department of Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

4. Department of Immunology, Medical School, Nanjing University, Nanjing, China

5. Department of Pathology, University of Hong Kong, Hong Kong, China

6. Department of Rheumatology, Medical University of South Carolina, Charleston, USA

7. Department of Rheumatology, Peking Union Medical College, Beijing, China

8. Department of Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China,

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 × 106UC-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.

Publisher

SAGE Publications

Subject

Rheumatology

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