Therapeutic effects of umbilical cord blood-derived mesenchymal stem cell transplantation in experimental lupus nephritis.
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.
Chang
Jei-Wen
JW
Division of Immunology and Nephrology, Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
Hung
Shun-Pei
SP
Wu
Hao-Hsiang
HH
Wu
Wen-Mien
WM
Yang
An-Hang
AH
Tsai
Hsin-Lin
HL
Yang
Ling-Yu
LY
Lee
Oscar K
OK
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D049109:Cell Proliferation; D036101:Cord Blood Stem Cell Transplantation; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008136:Longevity; D008181:Lupus Nephritis / Q000150:complications / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D008214:Lymphocytes / Q000473:pathology; D050527:Mesangial Cells / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D011507:Proteinuria / Q000150:complications / Q000503:physiopathology; D012598:Sclerosis / Q000150:complications / Q000473:pathology; D013154:Spleen / Q000473:pathology; D014470:Umbilical Cord / Q000166:cytology*
D000974:Antibodies, Antinuclear; D016207:Cytokines