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Tanshinone IIA-loaded aligned microfibers facilitate stem cell recruitment and capillary formation by inducing M2 macrophage polarization
Applied Materials Today ( IF 8.3 ) Pub Date : 2020-09-25 , DOI: 10.1016/j.apmt.2020.100841
Shan Gao , Lina Wang , Yu Zhang , Lan Li , Yunsha Zhang , Xiumei Gao , Jingyuan Mao , Lianyong Wang , Lichen Wang , Hongjun Wang , Meifeng Zhu , Guanwei Fan

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 1μM 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.



中文翻译:

丹参酮IIA加载对齐的超细纤维通过诱导M2巨噬细胞极化促进干细胞募集和毛细管形成

已经证明,直接植入无细胞的支架能够通过操纵免疫应答来促进组织再生,是再生医学的一种有前途的治疗策略。在这里,我们开发了丹参酮ⅡA(TanⅡA)持续释放的对齐的微纤维支架,以调节巨噬细胞的表型转变,从而促进干细胞的募集和毛细血管的形成。在RAW 264.7巨噬细胞中,装有1μMTanⅡA(AF-1)的对齐的微纤维支架显着下调促炎基因和蛋白质的表达,同时上调抗炎基因和蛋白质的表达从在AF-1支架上培养的巨噬细胞收集的条件培养基可增强骨髓来源的间充质干细胞(BMSC)的增殖和迁移,并调节其多种生物学功能,如RNA-Seq分析所示。此外,条件培养基还促进人脐静脉内皮细胞(HUVEC)增殖,迁移和管形成。通过利用大鼠皮下植入支架进一步证实了通过调节巨噬细胞表型转变来增强内源性干细胞募集和血管形成。这些结果支持使用载药的对齐的超细纤维支架,以实现免疫调节,以刺激干细胞募集和血管形成,这有可能导致无细胞,支架引导的组织成功再生。

更新日期:2020-09-25
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