Tanshinone IIA-loaded aligned microfibers facilitate stem cell recruitment and capillary formation by inducing M2 macrophage polarization
Tanshinone IIA-loaded aligned microfibers facilitate stem cell recruitment and capillary formation by inducing M2 macrophage polarization
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负载丹参酮 IIA 的排列微纤维通过诱导 M2 巨噬细胞极化促进干细胞募集和毛细血管形成
DOI：
10.1016/j.apmt.2020.100841
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发表时间：
2020-12-01
影响因子：
8.3
通讯作者：
Fan, Guanwei
中科院分区：
文献类型：
--
作者：
Gao, Shan;Wang, Lina;Fan, Guanwei
直接植入无细胞支架可以通过控制免疫反应来促进组织再生，已被证明是再生医学的一种有前途的治疗策略。在这里，我们开发了具有丹参酮IIA(Tan IIA)持续释放的定向微纤维支架，以调节巨噬细胞的表型转变，从而促进干细胞募集和毛细血管形成。在RAW 264.7巨噬细胞中，负载1MU M Tan IIA(AF-1)的定向微纤维支架显著下调促炎基因和蛋白的表达，同时上调抗炎基因和蛋白的表达。从AF-1支架上培养的巨噬细胞采集的条件培养液促进了骨髓间充质干细胞的增殖和迁移，并通过RNA-Seq分析证实了其多种生物学功能的调节。此外，条件培养液还促进人脐静脉内皮细胞(HUVEC)的增殖、迁移和管状形成。通过调节巨噬细胞的表型转变，进一步证实了通过大鼠皮下植入支架来促进内源性干细胞募集和血管形成。这些结果支持使用药物定向微纤维支架来实现免疫调节，以刺激干细胞招募和血管形成，这可能会导致成功的无细胞、支架引导的组织再生。(C)2020爱思唯尔有限公司。保留所有权利。
Direct implantation of cell-free scaffolds capable of promoting tissue regeneration by manipulating immune responses has proven to be a promising therapeutic strategy for regenerative medicine. Here, we developed aligned microfiber scaffolds with sustained release of tanshinone IIA (Tan IIA) to modulate macrophages phenotypic transition, which subsequently promoted stem cell recruitment and capillary formation. Aligned microfibers scaffolds loaded with 1 mu M Tan IIA (AF-1) significantly down-regulated the expression of proinflammatory genes and proteins, while they upregulated anti-inflammatory genes and proteins, in RAW 264.7 macrophages . Conditioned medium collected from macrophages cultured on AF-1 scaffolds enhanced bone marrow-derived mesenchymal stem cell (BMSC) proliferation and migration, and also regulated their multiple biological functions as evidenced by RNA-Seq assays. Moreover, the conditioned medium also promoted human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation. Enhancement of endogenous stem cell recruitment and vascularization by regulating macrophage phenotype transition was further confirmed by utilizing rat subcutaneous implantation of the scaffolds. These results support the use of drug-loaded aligned microfiber scaffolds to enable immune modulation to stimulate stem cell recruitment and vascularization, which could potentially result in successful cell-free, scaffold-guided tissue regeneration. (C) 2020 Elsevier Ltd. All rights reserved.