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

泼尼松或霉酚酸酯与间充质干细胞联合治疗 MRL.Faslpr 小鼠狼疮症状的效果

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作者:Hong Kyung Lee, Ki Hun Kim, Hyung Sook Kim, Ji Sung Kim, Jae Hee Lee, Ayoung Ji, Kyung Suk Kim, Tae Yong Lee, In Young Chang, Sang-Cheol Bae, Jin Tae Hong, Youngsoo Kim, Sang-Bae Han

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.

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