白细胞介素-1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。
IL-1 Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression.
作者信息
Nie He, An Fangmei, Mei Jie, Yang Cheng, Zhan Qiang, Zhang Qinglin
机构信息
Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214023, China.
Department of Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China.
出版信息
Stem Cells Int. 2020 Jul 7;2020:1498315. doi: 10.1155/2020/1498315. eCollection 2020.
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-1 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-1-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-1 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-1 pretreatment, and an increased migration ability towards SDF-1 that could be reversed by AMD3100 was found in Pre-MSCs.
CONCLUSION
IL-1 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.
背景
间充质干细胞（MSCs）对炎症性疾病具有强大的代谢和功能支持能力，可能是治疗急性肝衰竭（ALF）的有效策略。然而，如果进行预处理以增强其向受损肝脏的低迁移能力，MSCs的疗效仍可提高。本研究旨在确定白细胞介素-1（IL-1）预处理对ALF中MSCs的疗效和归巢能力的影响。
方法
采用全骨髓贴壁法分离并鉴定MSCs。在大鼠ALF模型中检测IL-1预处理的MSCs（Pre-MSCs）的疗效和归巢能力，并与MSCs和生理盐水进行比较。然后，进行蛋白质免疫印迹法检测MSCs和Pre-MSCs的c-Met和CXCR4表达，随后进行流式细胞术检测相关有意义指标。最后，通过Transwell迁移试验检测不同细胞和不同条件下的迁移能力。
结果
成功分离并培养出纯度理想的MSCs。与MSCs相比，Pre-MSCs在提高ALF大鼠生存率和肝功能方面具有显著更好的疗效。对受损肝组织的进一步分析表明，IL-1预处理显著增强了MSCs抑制肝坏死的疗效。此外，Pre-MSCs在抑制细胞凋亡和激活细胞增殖方面表现出更好的效果。用CM-Dil标记细胞的示踪实验结果证实，Pre-MSC组中有更多细胞迁移到受损肝脏。在机制方面，IL-1预处理显著增强了CXCR4表达，并且在Pre-MSCs中发现其对基质细胞衍生因子-1（SDF-1）的迁移能力增加，而这种增加可被AMD3100逆转。
结论
IL-1预处理可至少部分通过增加CXCR4表达来增强MSCs的归巢能力，并进一步提高MSCs对ALF的疗效。
Zotero 插件