Allogeneic adipose-derived stem cells suppress mTORC1 pathway in a murine model of systemic lupus erythematosus.

OBJECTIVE: The aim of our study was to investigate the efficacy of adipose-derived stem cells (ADSC) transplantation in systemic lupus erythematosus (SLE) and to determine the mechanism of ADSC transplantation.

METHODS: B6.MRL/lpr mice were administered ADSC intravenously every week from age 28 to 31 weeks, while the lupus control group and the normal control received phosphate buffered solution (PBS) on the same schedule.

RESULTS: Compared with the lupus control group, the ADSC treatment group had a significant improvement of histologic abnormalities, serologic abnormalities, and immunologic function. Anti-double-stranded DNA antibodies, spleen/weight ratio, deposits of C3/IgG in the kidney, and serum creatinine and blood urea nitrogen levels were significantly decreased with the transplantation of ADSC. A significant decrease of the Th17/CD4+ T cell ratio in the spleen, the serum IL-17 concentration, as well as renal IL-17 expression was observed in the ADSC treatment group. Western blot results also showed that ADSC treatment had a lower expression of protein kinase B (Akt), p-Akt, mTOR, p-mTOR, p70S6K, p-p70S6K, and HIF-1α.

CONCLUSION: ADSC treatment can prevent the development of lupus nephritis and significantly ameliorate already-established disease. ADSC treatment reduced Akt, mTOR, p70S6K, HIF-1α, and that this inhibition can avert IL-17-induced inflammation, suggesting that ADSC may be a promising treatment for SLE.