Mesenchymal stem cell secretome decreases the inflammatory response in annulus fibrosus organ cultures.
Mesenchymal stem cell secretome decreases the inflammatory response in annulus fibrosus organ cultures.
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DOI：
10.22203/ecm.v042a01
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发表时间：
2021-07
影响因子：
3.1
通讯作者：
C. Neidlinger-Wilke;A. Ekkerlein;R. Gonçalves;J. Ferreira;A. Ignatius;H. Wilke;G. Teixeira
中科院分区：
文献类型：
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作者：
C. Neidlinger-Wilke;A. Ekkerlein;R. Gonçalves;J. Ferreira;A. Ignatius;H. Wilke;G. Teixeira
基于间充质干细胞（MSC）的治疗方法已被提出用于治疗背痛和椎间盘退变，尽管对其作用机制的了解有限。在一个特制的装置中，分析了MSCs/其分泌组对纤维环（AF）细胞和组织的影响，AF- ocs暴露于上生理循环拉伸应变（CTS, 9%, 1 Hz, 3 h/d）和白细胞介素(IL)-1β。用MSC分泌组治疗CTS + il -1β刺激的AF-OCs 4 d，可下调炎症标志物[IL-6、IL-8、前列腺素内过氧化物合成酶2 (PTGS2)]、补体系统调节因子[分化集群（CD）46、CD55、CD59]和基质金属蛋白酶1的表达，也可下调金属蛋白酶组织抑制剂（TIMP-1、TIMP-2）和i型胶原的表达。与单独的CTS + IL-1β刺激相比，MSC分泌组处理的AF-OCs中MMP-3和胶原含量降低。处理后9 d，生物力学剥离力测试显示，MSC分泌组处理显著降低了环的粘附强度。总的来说，MSC分泌组对AF组织的影响比共培养的MSC更强。分泌组有助于降低CTS + IL-1β激活的AF细胞的炎症和分解代谢状态，并在补体系统的调节中发挥作用。然而，与单独的CTS + IL-1β刺激相比，它也导致基因/蛋白质水平上胶原蛋白的减少和AF机械强度的降低。因此，MSC分泌组的使用需要进一步研究其对椎间盘基质特性的影响。
Mesenchymal stem/stromal cell (MSC)-based therapies have been proposed for back pain and disc degeneration, despite limited knowledge on their mechanism of action. The impact of MSCs/their secretome on annulus fibrosus (AF) cells and tissue was analysed in bovine AF organ cultures (AF-OCs) exposed to upper-physiological cyclic tensile strain (CTS, 9 %, 1 Hz, 3 h/d) and interleukin (IL)-1β in a custom-made device. A 4 d treatment of the CTS + IL-1β-stimulated AF-OCs with MSC secretome downregulated the expression of inflammation markers [IL-6, IL-8, prostaglandin-endoperoxide synthase 2 (PTGS2)], complement system regulators [cluster of differentiation (CD)46, CD55, CD59] and matrix metalloproteinase 1 but also of tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and collagen type I. At the protein level, it was confirmed that IL-6, MMP-3 and collagen content was decreased in AF-OCs treated with the MSC secretome compared to the CTS + IL-1β stimulation alone. 9 d after treatment, a biomechanical peel-force test showed that the annular adhesive strength was significantly decreased by the MSC secretome treatment. Overall, MSC secretome had a stronger impact on AF tissue than MSCs in co-culture. The secretome contributed to a decrease in the inflammatory and catabolic status of AF cells activated by CTS + IL-1β and played a role in the regulation of the complement system. However, it also contributed to a decrease in collagen at the gene/protein level and in AF mechanical strength compared to the CTS + IL-1β stimulation alone. Therefore, the use of MSC secretome requires further investigation regarding its influence on disc matrix properties.