The clinical application of stem cells offers great promise as a potential avenue for therapeutic use in neurodegenerative diseases. However, cell loss after transplantation remains a major challenge, which currently plagues the field. On the basis of our previous findings that fibroblast growth factor 21 (FGF‐21) protected neurons from glutamate excitotoxicity and that upregulation of FGF‐21 in a rat model of ischemic stroke was associated with neuroprotection, we proposed that overexpression of FGF‐21 protects bone marrow‐derived mesenchymal stem cells (MSCs) from apoptosis. To test this hypothesis, we examined whether the detrimental effects of apoptosis can be mitigated by the transgenic overexpression of FGF‐21 in MSCs. FGF‐21 was transduced into MSCs by lentivirus and its overexpression was confirmed by quantitative polymerase chain reaction. Moreover, FGF‐21 overexpression did not stimulate the expression of other FGF family members, suggesting it does not activate a positive feedback system. The effects of hydrogen peroxide (H₂O₂), tumor necrosis factor‐α (TNF‐α), and staurosporine, known inducers of apoptosis, were evaluated in FGF‐21 overexpressing MSCs and mCherry control MSCs. Caspases 3 and 7 activity was markedly and dose‐dependently increased by all three stimuli in mCherry MSCs. FGF‐21 overexpression robustly suppressed caspase activation induced by H₂O₂ and TNF‐α, but not staurosporine. Moreover, the assessment of apoptotic morphological changes confirmed the protective effects of FGF‐21 overexpression. Taken together, these results provide compelling evidence that FGF‐21 plays a crucial role in protecting MSCs from apoptosis induced by oxidative stress and inflammation and merits further investigation as a strategy for enhancing the therapeutic efficacy of stem cell‐based therapies.

中文翻译：

---

成纤维细胞生长因子-21 (FGF-21) 的过表达保护间充质干细胞免受氧化应激和炎症诱导的半胱天冬酶依赖性细胞凋亡。

干细胞的临床应用为治疗神经退行性疾病的潜在途径提供了广阔的前景。然而，移植后细胞丢失仍然是一个主要挑战，目前困扰着该领域。基于我们之前的研究结果，即成纤维细胞生长因子 21 (FGF-21) 保护神经元免受谷氨酸兴奋性毒性，并且缺血性中风大鼠模型中 FGF-21 的上调与神经保护作用有关，我们提出 FGF-21 的过表达保护来自细胞凋亡的骨髓来源间充质干细胞 (MSCs)。为了验证这一假设，我们检查了 FGF-21 在 MSC 中的转基因过表达是否可以减轻细胞凋亡的不利影响。通过慢病毒将 FGF-21 转导到 MSCs 中，并通过定量聚合酶链反应证实其过度表达。此外，FGF-21 过表达不会刺激其他 FGF 家族成员的表达，表明它不会激活正反馈系统。过氧化氢（H₂ O ₂ )、肿瘤坏死因子-α (TNF-α) 和星形孢菌素（已知的凋亡诱导剂）在 FGF-21 过表达的 MSC 和 mCherry 对照 MSC 中进行了评估。caspase 3 和 7 活性在 mCherry MSCs 中被所有三种刺激显着且剂量依赖性地增加。FGF-21 过表达强烈抑制 H ₂ O ₂诱导的半胱天冬酶活化和 TNF-α，但不是星形孢菌素。此外，对凋亡形态变化的评估证实了 FGF-21 过表达的保护作用。总之，这些结果提供了令人信服的证据，表明 FGF-21 在保护 MSCs 免受氧化应激和炎症诱导的细胞凋亡方面起着至关重要的作用，值得进一步研究作为提高基于干细胞疗法疗效的策略。