Czekanska E M, Ralphs J R, Alini M, Stoddart M J
AO Research Institute, Clavadelerstrasse 8, CH 7270-Davos Platz,
Eur Cell Mater. 2014 Oct 23;28:320-34. doi: 10.22203/ecm.v028a22.
Stem cells have become the fundamental element in regenerative medicine due to their inherent potential to differentiate into various cell types, and the ability to produce various bioactive molecules, including growth factors, cytokines and extracellular matrix molecules. In vivo, the secretion of tropic factors is modulated by chemotactic and inflammatory factors. In this study, we analysed the influence of a 2 h stimulation of mesenchymal stem cells (MSCs) with interleukin-1β (IL1β), granulocyte-colony stimulating factor (GCSF), stromal cell-derived factor 1 (SDF1) and stem cell factor (SCF). Our results demonstrated that this short stimulation exerts pronounced effects on the expression of multiple cytokine genes and proteins in MSC cells 48 and 72 h later. IL1β strongly promoted the secretion of a wide range of proteins with chemotactic, proinflammatory and angiogenic properties, whereas SCF regulated the expression of proteins involved in proliferation, chondrogenesis and ECM regulation. This demonstrates that the changes in secretome can be directed towards a desired final functional outcome by selection of the most appropriate cytokine. Moreover, the expression pattern of Wnt signalling pathway components suggested the differential regulation of this pathway by IL1β and SCF. Altogether, the robust paracrine action of MSCs can be achieved within a just 2 h treatment, which would be feasible within the operating theatre during a single surgical procedure. These results suggest that integrating inflammatory modulation in bone tissue engineering, by modifying the MSC secretome by way of a short stimulus, would provide a more targeted approach than administering unmodified MSCs alone.
由于干细胞具有分化为各种细胞类型的内在潜力，以及产生包括生长因子、细胞因子和细胞外基质分子在内的各种生物活性分子的能力，它们已成为再生医学的基本要素。在体内，趋化因子和炎症因子可调节促生长因子的分泌。在本研究中，我们分析了用白细胞介素-1β（IL1β）、粒细胞集落刺激因子（GCSF）、基质细胞衍生因子1（SDF1）和干细胞因子（SCF）对间充质干细胞（MSC）进行2小时刺激的影响。我们的结果表明，这种短时间刺激在48和72小时后对MSC细胞中多种细胞因子基因和蛋白质的表达产生显著影响。IL1β强烈促进具有趋化、促炎和血管生成特性的多种蛋白质的分泌，而SCF调节参与增殖、软骨生成和细胞外基质调节的蛋白质的表达。这表明通过选择最合适的细胞因子，可以将分泌组的变化导向期望的最终功能结果。此外，Wnt信号通路成分的表达模式表明IL1β和SCF对该通路有不同的调节作用。总之，仅2小时的处理就能实现MSC强大的旁分泌作用，这在单次外科手术的手术室中是可行的。这些结果表明，通过短时间刺激修饰MSC分泌组，将炎症调节整合到骨组织工程中，比单独施用未修饰的MSC提供了一种更具针对性的方法。
