CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor-associated macrophages-educated reparative macrophages promote diabetic wound healing.
Tumor-associated macrophages-educated reparative macrophages promote diabetic wound healing.
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不愈合的糖尿病伤口伴有持续性炎症和血管损伤,常规治疗无效,需要综合干预。在此,受肿瘤相关巨噬细胞(TAMs)在肿瘤发展中产生大量免疫抑制和促增殖因子的启发,我们通过用TAMs条件培养基(TAMs-CM)培养正常巨噬细胞,生成巨噬细胞以重现TAMs的修复功能。这些经TAMs教育的巨噬细胞(TAMEMs)在体外抑制炎症、刺激血管生成和激活成纤维细胞方面优于主要巨噬细胞表型(M0、M1或M2)。当递送至糖尿病小鼠的皮肤伤口时,TAMEMs有效促进愈合。基于TAMs-CM的组成,我们进一步重建了一种九因子混合物,以将人原代单核细胞训练为TAMEMs C-h,其完全类似于TAMEMs的功能,而不使用肿瘤成分,从而具有更高的安全性并能够制备自体细胞。我们的研究表明,在非肿瘤细胞中重现TAMs独特的修复活性可以产生一种有效的细胞治疗方法,具有高转化潜力,适用于再生医学。
Nonhealing diabetic wounds, with persistent inflammation and damaged vasculature, have failed conventional treatments and require comprehensive interference.
Here, inspired by tumor-associated macrophages (TAMs) that produce abundant immunosuppressive and proliferative factors in tumor development, we generate macrophages to recapitulate TAMs' reparative functions, by culturing normal macrophages with TAMs' conditional medium (TAMs-CM). These TAMs-educated macrophages (TAMEMs) outperform major macrophage phenotypes (M0, M1, or M2) in suppressing inflammation, stimulating angiogenesis, and activating fibroblasts in vitro.
When delivered to skin wounds in diabetic mice, TAMEMs efficiently promote healing. Based on TAMs-CM's composition, we further reconstitute a nine-factor cocktail to train human primary monocytes into TAMEMs C-h , which fully resemble TAMEMs' functions without using tumor components, thereby having increased safety and enabling the preparation of autologous cells.
Our study demonstrates that recapitulating TAMs' unique reparative activities in nontumor cells can lead to an effective cell therapeutic approach with high translational potential for regenerative medicine.
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