Department of Biomedical Engineering, College of Engineering, Peking University, Room 206, Fangzheng Building, 298 Chengfu Road, Haidian District, Beijing, 100871, China.
Department of Biomedical Engineering, College of Engineering, Peking University, Room 206, Fangzheng Building, 298 Chengfu Road, Haidian District, Beijing, 100871, China.
Biomaterials. 2017 Oct;141:74-85. doi: 10.1016/j.biomaterials.2017.06.028. Epub 2017 Jun 23.
While the studies on the material interaction with mesenchymal stem cells (MSCs) have been mainly focused on the ability of materials to provide environment to regulate cell viability, proliferation or differentiation, the therapeutic effects of MSC-material constructs may result from the secretion of immunomodulatory and angiogenic cytokines from MSCs. Here, electrospun scaffolds composed of fibers in random, aligned and mesh-like patterns were fabricated, and the paracrine behavior of adipose-derived MSCs (Ad-MSCs) on the scaffolds were investigated in comparison to the cell culture via conventional microplates. It was found that the Ad-MSCs on the electrospun fibers produced significantly higher levels of anti-inflammatory and pro-angiogenic cytokines compared to those cultured on microplates. The enhanced modulatory effects of the secreted products of Ad-MSCs on fibrous electrospun scaffolds were also proven in the cultures of endothelial cells and the LPS-stimulated macrophages, with three types of scaffolds showing distinct influences on the paracrine function of Ad-MSCs. In a skin excisional wound-healing model in rat, the conditioned medium collected from the MSC-scaffold system accelerated the wound closure, promoted the macrophage recruitment and enhanced the polarization of macrophages toward the pro-healing phenotype in the wound bed. Our study demonstrates that the fibrous topography of scaffolds is a key material property that modulates the paracrine function of cells. The discovery elucidates a new aspect of material functions, laying the foundation for developing scaffold materials to promote tissue regeneration/repair through guiding the paracrine signaling network.
虽然关于材料与间充质干细胞（MSCs）相互作用的研究主要集中在材料提供调节细胞活力、增殖或分化的环境的能力上，但 MSC-材料构建体的治疗效果可能源于 MSCs 分泌的免疫调节和血管生成细胞因子。在这里，制备了由随机、对齐和网状图案纤维组成的静电纺丝支架，并通过传统的微孔板比较了支架上脂肪来源的间充质干细胞（Ad-MSCs）的旁分泌行为与细胞培养。结果发现，与在微孔板上培养的细胞相比，静电纺丝纤维上的 Ad-MSCs 产生的抗炎和促血管生成细胞因子水平显著更高。在培养内皮细胞和 LPS 刺激的巨噬细胞的过程中，还证明了 Ad-MSCs 分泌产物对纤维状静电纺丝支架的增强调节作用，三种支架对 Ad-MSCs 的旁分泌功能有明显影响。在大鼠皮肤切除性伤口愈合模型中，从 MSC-支架系统收集的条件培养基加速了伤口闭合，促进了巨噬细胞募集，并增强了巨噬细胞向伤口床中促愈合表型的极化。我们的研究表明，支架的纤维状形貌是调节细胞旁分泌功能的关键材料特性。这一发现阐明了材料功能的一个新方面，为通过指导旁分泌信号网络来开发促进组织再生/修复的支架材料奠定了基础。
