Effect of a Combination of Prednisone or Mycophenolate Mofetil and Mesenchymal Stem Cells on Lupus Symptoms in MRL.Fas^lpr Mice

Abstract

The combination of immunosuppressants and mesenchymal stem cells (MSCs) is a promising therapeutic strategy for systemic lupus erythematosus, since this approach reduces doses of immunosuppressants while maintaining the same therapeutic outcome. However, it is unavoidable for MSCs to be exposed to immunosuppressants. Here, we examined the combination effect of prednisone (PD) or mycophenolate mofetil (MMF) and MSCs. We showed that PD or MMF in combination with MSCs showed better therapeutic effect than single therapy in lupus-prone MRL.Faslpr mice, as assessed by using the following readouts: prolongation of survival, decrease in anti-dsDNA and total IgG levels in serum, decrease in cytokine gene expression in spleen cells, and decrease in inflammatory cell infiltration into the kidney. In vitro, immunosuppressants and MSCs inhibited T cell proliferation in a synergistic manner. However, immunosuppressants did not affect MSC viability and functions such as TGF-β1 and PGE2 production, migration, and immunosuppressive capacity. In summary, our study demonstrates that a combination of immunosuppressants and MSCs is a good strategy to reduce the side effects of PD and MMF without the loss of therapeutic outcome.

Effect of Human Mesenchymal Stem Cells on Xenogeneic T and B Cells Isolated from Lupus-Prone MRL.Faslpr Mice

“…Lee et al [14] showed that the transfer of hMSCs increased MRL.Fas lpr mouse survival, decreased T cell infiltration in the kidneys, and reduced T cell cytokine expression. Lee et al [24] also showed that hMSCs in combination with prednisone or mycophenolate mofetil had a better therapeutic effect than single therapy in MRL.Fas lpr mice; the following readouts were used in this study: prolongation of survival, decrease in anti-dsDNA and total IgG levels in serum, decrease in cytokine gene expression in spleen cells, and decrease in inflammatory cell infiltration into the kidney. Liu et al [25] showed that hMSCs reduced proteinuria level, serum anti-dsDNA antibody level, and renal damage in MRL.Fas lpr mice.…”

Phorbol ester activates human mesenchymal stem cells to inhibit B cells and ameliorate lupus symptoms in MRL.Faslpr mice

“…To measure B cell proliferation, cells were pulsed with [ 3 H]-thymidine (113 Ci/nmol; NEN, Boston, MA, USA) at a concentration of 1 μCi/well for the last 18 h and were harvested on day 3 using an automated cell harvester (Inotech, Dottikon, Switzerland). The amount of [ 3 H]-thymidine incorporated into the cells was measured using a Wallac Microbeta scintillation counter (Wallac, Turku, Finland) 3 .…”

“…Mesenchymal stem cells (MSCs) are multipotent adult stem cells that have emerged as a promising therapy for the treatment of SLE. Adoptive transfer of MSCs to lupus-prone MRL .Fas lpr mice increased their survival and decreased anti-dsDNA antibody level and nephritis 3 - 9 . In clinical studies, MSCs improved renal functions and decreased autoantibody production 10 - 15 .…”

Mesenchymal Stem Cells Ameliorate Renal Inflammation in Adriamycin-induced Nephropathy

“…Whole cell lysates were prepared as previously described (23). Detergent-insoluble material was removed, and equal amounts of protein were fractionated by 10% SDS-PAGE and transferred to pure nitrocellulose membranes.…”