Caires Hugo R, Esteves Tiago, Quelhas Pedro, Barbosa Mário A, Navarro Melba, Almeida Catarina R
i3S-Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal INEB-Instituto de Engenharia Biomédica, Porto, Portugal ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
i3S-Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal INEB-Instituto de Engenharia Biomédica, Porto, Portugal Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, s/n, 4200-465 Porto, Portugal.
J R Soc Interface. 2016 Sep;13(122). doi: 10.1098/rsif.2016.0570.
Despite the importance of immune cell-biomaterial interactions for the regenerative outcome, few studies have investigated how distinct three-dimensional biomaterials modulate the immune cell-mediated mesenchymal stem/stromal cells (MSC) recruitment and function. Thus, this work compares the response of varied primary human immune cell populations triggered by different model scaffolds and describes its functional consequence on recruitment and motility of bone marrow MSC. It was found that polylactic acid (PLA) and chitosan scaffolds lead to an increase in the metabolic activity of macrophages but not of peripheral blood mononuclear cells (PBMC), natural killer (NK) cells or monocytes. PBMC and NK cells increase their cell number in PLA scaffolds and express a secretion profile that does not promote MSC recruitment. Importantly, chitosan increases IL-8, MIP-1, MCP-1 and RANTES secretion by macrophages while PLA stimulates IL-6, IL-8 and MCP-1 production, all chemokines that can lead to MSC recruitment. This secretion profile of macrophages in contact with biomaterials correlates with the highest MSC invasion. Furthermore, macrophages enhance stem cell motility within chitosan scaffolds by 44% but not in PLA scaffolds. Thus, macrophages are the cells that in contact with engineered biomaterials become activated to secrete bioactive molecules that stimulate MSC recruitment.
尽管免疫细胞与生物材料的相互作用对再生结果很重要，但很少有研究探讨不同的三维生物材料如何调节免疫细胞介导的间充质干细胞（MSC）募集和功能。因此，这项工作比较了不同模型支架引发的各种原代人免疫细胞群体的反应，并描述了其对骨髓MSC募集和迁移的功能影响。研究发现，聚乳酸（PLA）和壳聚糖支架会导致巨噬细胞代谢活性增加，但不会导致外周血单核细胞（PBMC）、自然杀伤（NK）细胞或单核细胞代谢活性增加。PBMC和NK细胞在PLA支架中的细胞数量增加，并表达一种不促进MSC募集的分泌谱。重要的是，壳聚糖会增加巨噬细胞分泌白细胞介素-8（IL-8）、巨噬细胞炎性蛋白-1（MIP-1）、单核细胞趋化蛋白-1（MCP-1）和调节激活正常T细胞表达和分泌因子（RANTES），而PLA则刺激白细胞介素-6（IL-6）、IL-8和MCP-1的产生，所有这些趋化因子都可导致MSC募集。与生物材料接触的巨噬细胞的这种分泌谱与最高的MSC侵袭相关。此外，巨噬细胞使壳聚糖支架内的干细胞迁移率提高了44%，但在PLA支架中则没有。因此，巨噬细胞是与工程生物材料接触后被激活以分泌刺激MSC募集的生物活性分子的细胞。
