INEB-Instituto de Engenharia Biomédica, Biomaterials Division, NEWTherapies Group, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
J R Soc Interface. 2012 Feb 7;9(67):261-71. doi: 10.1098/rsif.2011.0357. Epub 2011 Jul 13.
An exacerbated inflammatory response questions biomaterial biocompatibility, but on the other hand, inflammation has a central role in the regulation of tissue regeneration. Therefore, it may be argued that an 'ideal' inflammatory response is crucial to achieve efficient tissue repair/regeneration. Natural killer (NK) cells, being one of the first populations arriving at an injury site, can have an important role in regulating bone repair/regeneration, particularly through interactions with mesenchymal stem/stromal cells (MSCs). Here, we studied how biomaterials designed to incorporate inflammatory signals affected NK cell behaviour and NK cell-MSC interactions. Adsorption of the pro-inflammatory molecule fibrinogen (Fg) to chitosan films led to a 1.5-fold increase in adhesion of peripheral blood human NK cells, without an increase in cytokine secretion. Most importantly, it was found that NK cells are capable of stimulating a threefold increase in human bone marrow MSC invasion, a key event taking place in tissue repair, but did not affect the expression of the differentiation marker alkaline phosphatase (ALP). Of significant importance, this NK cell-mediated MSC recruitment was modulated by Fg adsorption. Designing novel biomaterials leading to rational modulation of the inflammatory response is proposed as an alternative to current bone regeneration strategies.
炎症反应加剧会影响生物材料的生物相容性，但另一方面，炎症在组织再生的调控中起着核心作用。因此，可以说，实现有效组织修复/再生的“理想”炎症反应至关重要。自然杀伤 (NK) 细胞是最早到达损伤部位的细胞群之一，在调节骨修复/再生方面可能具有重要作用，特别是通过与间充质干细胞/基质细胞 (MSC) 的相互作用。在这里，我们研究了设计用于纳入炎症信号的生物材料如何影响 NK 细胞的行为和 NK 细胞-MSC 相互作用。纤维蛋白原 (Fg) 等促炎分子的吸附导致外周血人 NK 细胞的黏附增加了 1.5 倍，细胞因子分泌没有增加。最重要的是，研究发现 NK 细胞能够刺激人骨髓 MSC 浸润增加三倍，这是组织修复过程中的一个关键事件，但不会影响碱性磷酸酶 (ALP) 的分化标记物的表达。非常重要的是，这种 NK 细胞介导的 MSC 募集可通过 Fg 吸附进行调节。提出设计新型生物材料以合理调节炎症反应作为当前骨再生策略的替代方法。
