Mussel-Inspired Nanostructures Potentiate the Immunomodulatory Properties and Angiogenesis of Mesenchymal Stem Cells
Mussel-Inspired Nanostructures Potentiate the Immunomodulatory Properties and Angiogenesis of Mesenchymal Stem Cells
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受贻贝启发的纳米结构增强间充质干细胞的免疫调节特性和血管生成
DOI：
10.1021/acsami.8b22017
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发表时间：
2019-05-15
影响因子：
9.5
通讯作者：
Wang, Jinwu
中科院分区：
文献类型：
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作者：
Li, Tao;Ma, Hongshi;Wang, Jinwu
骨髓间充质干细胞（mesenchymal stem cells，MSCs）材料构建体的治疗作用主要来自于MSCs分泌的营养因子，尤其是免疫调节因子和血管生成因子。最近的研究结果表明，这些材料的地形线索在调节旁分泌功能的MSC的意义。在这里，我们开发了功能化的三维打印生物陶瓷（BC）支架与贻贝启发的表面涂层，以调节旁分泌功能的脂肪来源的骨髓间充质干细胞（Ad-MSCs）。我们发现，Ad-MSCs培养在聚多巴胺修饰的BC支架（DOPA-BC）显着产生更多的免疫调节和促血管生成因子相比，那些培养在BC支架或微孔板。进行功能测定，如内皮祖细胞迁移、管形成和巨噬细胞极化，以确认在DOPA-BC支架上培养的Ad-MSC分泌的营养因子的增强的旁分泌功能。进一步的研究表明，粘着斑激酶和细胞外信号相关的激酶信号是所需的机械转导途径，通过该途径，贻贝启发的表面刺激Ad-MSCs的旁分泌效应。在大鼠糖尿病皮肤缺损愈合模型中，从在DOPA-BC上培养的Ad-MSC接收的条件培养基加速伤口闭合，增强血管形成，并促进伤口床中的巨噬细胞从促炎性M1转变为促愈合和抗炎性M2表型。这些结果表明，含有聚多巴胺的生物启发涂层是增强MSC旁分泌功能的有效方法。我们的发现阐明了一种通过引导旁分泌信号网络来加速组织再生的新策略。
The therapeutic effects of mesenchymal stem cells (MSCs)-material constructs mainly come from the secretion of trophic factors from MSCs, especially the immunomodulatory and angiogenic cytokines. Recent findings indicate the significance of topographical cues from these materials in modulating paracrine functions of MSCs. Here, we developed functionalized three-dimensional-printed bioceramic (BC) scaffolds with a mussel-inspired surface coating in order to regulate the paracrine function of adipose-derived MSCs (Ad-MSCs). We found that Ad-MSCs cultured on polydopamine-modified BC scaffolds (DOPA-BC) significantly produced more immunomodulatory and pro-angiogenic factors when compared with those cultured on BC scaffolds or microplates. Functional assays, such as endothelial progenitor cells migration, tube formation, and macrophage polarization, were performed to confirm the enhanced paracrine functions of the secreted trophic factors from Ad-MSCs cultured on DOPA-BC scaffolds. Further investigation identified that both focal adhesion kinase- and extracellular signal-related kinase signaling were the required mechano-transduction pathways through which the mussel-inspired surface stimulated the paracrine effect of Ad-MSCs. In a diabetic skin-defect-healing model in rats, conditioned medium received from the Ad-MSCs cultured on DOPA-BC sped wound closure, enhanced vascularization, and promoted macrophage switching from a proinflammatory M1 to a pro healing and anti-inflammatory M2 phenotype in the wound bed. These results demonstrate that a bio-inspired coating with polydopamine represents an effective method to enhance the paracrine function of MSCs. Our findings illustrate a novel strategy to accelerate tissue regeneration by guiding the paracrine-signaling network.