Macrophages promote vasculogenesis during retinal neovascularization (RNV) by increasing the recruitment and differentiation of bone marrow-derived cells (BMCs). Different subtypes of macrophages (M1 and M2 macrophages) are associated with RNV. However, the mechanism underlying the regulation of BMCs by different macrophage subtypes during RNV remains unclear. In the present study, we investigated the role and mechanism of action of different macrophage subtypes that regulate BMCs during the development of RNV. The retinal avascular area and neovascularization (NV) tuft area in M2 macrophage group in vivo were the largest compared to those in the control phosphate buffer saline (PBS), unpolarized-M0, and M1 macrophage groups. The number of recruited green fluorescent protein (GFP)-positive BMCs and the degree of differentiation of BMCs into CD31-positive endothelial cells (ECs) and alpha-smooth muscle actin (α-SMA)-positive smooth muscle cells (SMCs) were higher in the M2 macrophage group than in the other groups. M2-conditional medium (M2-CM) affected the in vitro migration and activation of bone marrow mesenchymal stem cells (BMSCs, a subset of BMCs) more than M1-CM. The expression of stromal cell-derived factor-1 (SDF-1) and vascular endothelial growth factor (VEGF) in M2 macrophages and BMSCs cultured with M2-CM was also higher than that in M1 macrophages and BMSCs cultured with M1-CM. Migration of BMSCs was reduced after inhibiting the SDF-1 signaling pathway. Our results indicate that M2 macrophages may express significantly higher levels of SDF-1 and VEGF than M1 macrophages, thus regulating the recruitment and differentiation of BMCs and further aggravating vasculogenesis during RNV.

中文翻译：

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M2巨噬细胞通过SDF-1/VEGF调节骨髓衍生细胞促进视网膜新生血管形成过程中的血管生成

巨噬细胞通过增加骨髓衍生细胞 (BMC) 的募集和分化来促进视网膜新生血管 (RNV) 血管生成。不同亚型的巨噬细胞（M1 和 M2 巨噬细胞）与 RNV 相关。然而，RNV 期间不同巨噬细胞亚型对 BMC 的调控机制尚不清楚。在本研究中，我们研究了在 RNV 发展过程中调节 BMC 的不同巨噬细胞亚型的作用和作用机制。与对照磷酸盐缓冲盐水 (PBS)、非极化-M0 和 M1 巨噬细胞组相比，体内 M2 巨噬细胞组的视网膜无血管区域和新生血管 (NV) 簇区域最大。募集的绿色荧光蛋白 (GFP) 阳性 BMC 的数量和 BMC 向 CD31 阳性内皮细胞 (EC) 和 α-平滑肌肌动蛋白 (α-SMA) 阳性平滑肌细胞 (SMC) 的分化程度较高在 M2 巨噬细胞组中比在其他组中。M2 条件培养基（M2-CM）对骨髓间充质干细胞（BMSC，BMC 的一个子集）的体外迁移和活化的影响大于 M1-CM。基质细胞衍生因子-1（SDF-1）和血管内皮生长因子（VEGF）在 M2-CM 培养的 M2 巨噬细胞和 BMSC 中的表达也高于 M1 巨噬细胞和 M1-CM 培养的 BMSC。抑制 SDF-1 信号通路后，BMSCs 的迁移减少。