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

Lupus. 2010 Nov;19(13):1502-14. doi: 10.1177/0961203310373782. Epub 2010 Jul 20.

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 × 10(6) 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / metabolism
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Transplantation
  • Chemokine CCL2 / antagonists & inhibitors
  • Creatinine / blood
  • Female
  • Gene Expression Regulation
  • HMGB1 Protein / antagonists & inhibitors
  • Humans
  • Lupus Nephritis / pathology
  • Lupus Nephritis / therapy*
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mice
  • Mice, Inbred MRL lpr
  • Proteinuria / etiology
  • Proteinuria / therapy
  • Umbilical Cord / cytology*

Substances

  • Antibodies, Antinuclear
  • Chemokine CCL2
  • HMGB1 Protein
  • Creatinine