Rapamycin reverses the senescent phenotype and improves immunoregulation of mesenchymal stem cells from MRL/lpr mice and systemic lupus erythematosus patients through inhibition of the mTOR signaling pathway

Citations Over TimeTop 10% of 2016 papers

Abstract

We have shown that bone marrow (BM)-derived mesenchymal stem cells (BM-MSCs) from SLE patients exhibit senescent behavior and are involved in the pathogenesis of SLE. The aim of this study was to investigate the effects of rapamycin (RAPA) on the senescences and immunoregulatory ability of MSCs of MRL/lpr mice and SLE patients and the underlying mechanisms. Cell morphology, senescence associated β-galactosidase (SA-β-gal) staining, F-actin staining were used to detect the senescence of cells. BM-MSCs and purified CD4+ T cells were co-cultured indirectly. Flow cytometry was used to inspect the proportion of regulatory T (Treg) /T helper type 17 (Th17). We used small interfering RNA (siRNA) to interfere the expression of mTOR, and detect the effects by RT-PCR, WB and immunofluorescence. Finally, 1x106 of SLE BM-MSCs treated with RAPA were transplanted to cure the 8 MRL/lpr mice aged 16 weeks for 12 weeks. We demonstrated that RAPA alleviated the clinical symptoms of lupus nephritis and prolonged survival in MRL/lpr mice. RAPA reversed the senescent phenotype and improved immunoregulation of MSCs from MRL/lpr mice and SLE patients through inhibition of the mTOR signaling pathway. Marked therapeutic effects were observed in MRL/lpr mice following transplantation of BM-MSCs from SLE patients pretreated with RAPA.

Related Papers

• → Mesenchymal stem cell therapy in treatment of erectile dysfunction: Autologous or allogeneic cell sources?(2014)32 cited
• → PI3K/Akt/mTOR Pathway: A Growth and Proliferation Pathway(2009)18 cited
• → Mesenchymal Stem/Stromal Cells: ASSESSING THE SAFETY AND TOXICITY OF VERY HIGH DOSES OF ALLOGENEIC HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS(2023)1 cited
• → Mesenchymal Stem/Stromal Cells: COMMENCEMENT OF FIRST-IN-HUMAN FOR CLINICAL TRIAL OF ADIPOSE TISSUE DERIVED ALLOGENEIC MESENCHYMAL STEM CELL (ADMSC) SHEETS FOR RETINAL DISEASES(2023)
• → [Research Progress on the Mechanism of PI3K/AKT/mTOR Signaling Pathway in Multiple Myeloma --Review].(2024)