Transplantation of umbilical cord mesenchymal stem cells alleviates lupus nephritis in MRL/lpr mice.
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.
Gu
Z
Z
Department of Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Akiyama
K
K
Ma
X
X
Zhang
H
H
Feng
X
X
Yao
G
G
Hou
Y
Y
Lu
L
L
Gilkeson
G S
GS
Silver
R M
RM
Zeng
X
X
Shi
S
S
Sun
L
L
D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors; D003404:Creatinine / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors; D006801:Humans; D008181:Lupus Nephritis / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011507:Proteinuria / Q000209:etiology / Q000628:therapy; D014470:Umbilical Cord / Q000166:cytology*
D000974:Antibodies, Antinuclear; D018932:Chemokine CCL2; D024243:HMGB1 Protein; D003404:Creatinine