Background

The poor survival rate and undesirable homing of transplanted stem cells are the major challenges in stem cell therapy. Addressing the challenge would improve the therapeutic efficacy of these cells. Dimethyl fumarate (DMF) is an anti-inflammatory drug that exerts its effects through the activation of the nuclear factor erythroid 2–related factor 2 (Nrf2) pathway. Therefore, its cytoprotective effects on human adipose-derived MSCs (hASCs) against various oxidative stresses have been investigated in this study.

Methods and results

hASCs were cultured with different concentrations of DMF to evaluate the cytotoxicity of DMF on hASCs using Cell Counting Kit-8 (CCK-8). Besides, the migration ability of the cells after DMF treatment was evaluated using the Transwell method. Furthermore, the expression of HO-1 and NQO-1 was determined using RT-PCR. The cytoprotective effects of DMF on hASCs against the oxidative stress caused by H₂O₂ and Ultra Violet (UV) were evaluated by assessing cell proliferation and apoptosis. Our results demonstrated that under oxidative stress conditions induced by H₂O₂ and UV, DMF increased the survival rate and proliferation of the cells and prevented apoptosis. Moreover, the expression of HO-1 and NQO-1 was upregulated in hASCs pretreated with DMF which confirms the activation of the Nrf2 pathway. However, DMF significantly decreased migration in hADSCs (P < 0.0001).

Conclusion

Our findings indicate that DMF enhances the proliferation capability and viability of hASCs and prevents their apoptosis in harsh stressful microenvironments. However, the applicability of DMF as a cytoprotective factor for the augmentation of hASCs requires in-depth preclinical and clinical studies.

中文翻译：

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富马酸二甲酯可防止人脂肪来源的间充质干细胞中由氧化应激介导的细胞毒性和细胞凋亡

背景

移植干细胞的低存活率和不良归巢是干细胞治疗的主要挑战。解决这一挑战将提高这些细胞的治疗效果。富马酸二甲酯 (DMF) 是一种抗炎药，通过激活核因子红细胞 2 相关因子 2 (Nrf2) 途径发挥作用。因此，本研究研究了其对人类脂肪来源的 MSCs (hASCs) 对抗各种氧化应激的细胞保护作用。

方法和结果

hASCs 与不同浓度的 DMF 一起培养，以使用 Cell Counting Kit-8 (CCK-8) 评估 DMF 对 hASCs 的细胞毒性。此外，使用 Transwell 方法评估 DMF 处理后细胞的迁移能力。此外，使用 RT-PCR 测定 HO-1 和 NQO-1 的表达。通过评估细胞增殖和凋亡来评估DMF 对 hASCs 对 H ₂ O ₂和紫外线 (UV) 引起的氧化应激的细胞保护作用。我们的结果表明，在 H ₂ O _{2诱导的氧化应激条件下}和UV、DMF增加细胞的存活率和增殖并阻止细胞凋亡。此外，用 DMF 预处理的 hASCs 中 HO-1 和 NQO-1 的表达上调，这证实了 Nrf2 途径的激活。然而，DMF 显着降低了 hADSCs 的迁移（P < 0.0001）。

结论

我们的研究结果表明，DMF 增强了 hASCs 的增殖能力和活力，并防止它们在恶劣的压力微环境中凋亡。然而，DMF 作为增强 hASCs 的细胞保护因子的适用性需要深入的临床前和临床研究。