Background. Mesenchymal stem cells (MSCs), with the powerful metabolic and functional supporting abilities for inflammatory diseases, may be an effective therapeutic strategy for acute liver failure (ALF). However, the efficacy of MSCs can still be promoted if pretreatment is applied to enhance their poor migration towards the damaged liver. The purpose of this study is to determine the effect of IL-1β pretreatment on the efficacy and homing ability of MSCs in ALF. Methods. MSCs were isolated by the whole bone marrow adherence method and characterized. The efficacy and homing ability of IL-1β-pretreated MSCs (Pre-MSCs) were examined in a rat ALF model and compared with that of MSCs and normal saline. Then, Western blot was performed to detect the c-Met and CXCR4 expression of MSCs and Pre-MSCs and followed by flow cytometry to detect the meaningful indicators. Finally, the migration abilities of different cells and different conditions were tested by the Transwell migration assay. Results. MSCs of ideal purity were successfully isolated and cultured. Comparing with MSCs, Pre-MSCs had significantly better efficacy on improving the survival rate and liver function of ALF rats. Further analyses of damaged liver tissues showed that IL-1β pretreatment significantly enhanced the efficacy of MSCs on suppressing liver necrosis. Besides, Pre-MSCs exhibited better effects in inhibiting apoptosis and activating proliferation. The results of tracing experiments with CM-Dil-labeled cells confirmed that more cells migrated to the damaged liver in the Pre-MSC group. In terms of mechanism, the CXCR4 expression was significantly enhanced by IL-1β pretreatment, and an increased migration ability towards SDF-1 that could be reversed by AMD3100 was found in Pre-MSCs. Conclusion. IL-1β pretreatment could enhance the homing ability of MSCs at least partially by increasing the expression of CXCR4 and further improve the efficacy of MSCs on ALF.

中文翻译：

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IL-1β预处理通过增强CXCR4表达提高间充质干细胞对急性肝衰竭的疗效。

背景。间充质干细胞（MSCs）具有强大的炎症性疾病代谢和功能支持能力，可能是急性肝衰竭（ALF）的有效治疗策略。然而，如果应用预处理以增强其向受损肝脏的不良迁移，仍然可以提高MSCs的功效。本研究的目的是确定 IL-1 β预处理对 ALF 中 MSCs 疗效和归巢能力的影响。方法。采用全骨髓贴壁法分离MSCs并进行表征。IL- 1β的功效和归巢能力在大鼠 ALF 模型中检查预处理的 MSCs (Pre-MSCs)，并与 MSCs 和生理盐水的比较。然后，进行Western blot检测MSCs和Pre-MSCs的c-Met和CXCR4表达，随后用流式细胞仪检测有意义的指标。最后，通过Transwell迁移试验测试了不同细胞和不同条件下的迁移能力。结果。成功分离和培养了理想纯度的 MSC。与MSCs相比，Pre-MSCs在提高ALF大鼠存活率和肝功能方面的疗效显着提高。对受损肝组织的进一步分析表明，IL-1 β预处理显着增强了MSCs抑制肝坏死的功效。此外，Pre-MSCs在抑制细胞凋亡和激活增殖方面表现出更好的效果。CM-Dil 标记细胞的示踪实验结果证实，在 Pre-MSC 组中更多的细胞迁移到受损的肝脏。在机制方面，IL-1 β预处理显着增强了 CXCR4 的表达，并且在 Pre-MSCs 中发现了可以被 AMD3100 逆转的向 SDF-1 的迁移能力增加。结论。IL- 1β预处理可以通过增加CXCR4的表达至少部分地增强MSCs的归巢能力，并进一步提高MSCs对ALF的功效。