Mesenchymal stem cell transplantation can restore lupus disease-associated miRNA expression and Th1/Th2 ratios in a murine model of SLE

C3.MRL-Faslpr/J mice spontaneously develop high titers of anti-dsDNA, mild glomerular nephritis,
and severe lymphoproliferation symptoms. This study aimed to compare the effects of longterm
serial administration of human adipose tissue-derived mesenchymal stem cells (ASCs), and
cyclophosphamide treatment in C3.MRL-Faslpr/J mice using a murine SLE model. C3.MRL-Faslpr/J
mice were divided into saline (C), cyclophosphamide (Y), and ASC (H) treatment groups. Backgroundmatched
control C3H mice treated with saline (N) were also compared. The Y group showed the greatest
improvement in disease parameters, but with damaged trabecular integrity. ASC transplantation
reduced anti-dsDNA levels, glomerular C3 deposition and CD138 proportion significantly, without
trabecular damage. Furthermore, both cyclophosphamide and ASC treatment significantly decreased
the ratio of Th1/Th2 compared with the saline-treatment. The expression levels of miR-31-5p, miR-
96-5p, miR-182-5p, miR-183-5p, and miR-379-5p were significantly higher, while those of miR150-5p
were significantly lower in the C group than in the N group. The expression levels of miR-96-5p,
miR-182-5p in the Y and H groups were significantly lower than in the C group. Thus, treatment with
cyclophosphamide or ASC can change miRNAs and decrease miR-96-5p and miR-182-5p expression,
as well as decreasing the CD138 proportion and the Th1/Th2 ratio, which might be involved in the
therapeutic mechanism.