Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
Wound Repair Regen. 2013 Jan-Feb;21(1):44-54. doi: 10.1111/j.1524-475X.2012.00858.x. Epub 2012 Nov 5.
In adults, repair of deeply injured skin wounds results in the formation of scar tissue, whereas in embryos wounds heal almost scar-free. Macrophages are important mediators of wound healing and secrete cytokines and tissue remodeling enzymes. In contrast to host defense mediated by inflammatory M1 macrophages, wound healing and tissue repair involve regulatory M2/M2-like macrophages. Embryonic/fetal macrophages are M2-like, and this may promote scar-free wound healing. In the present study, we asked whether atopical application of ex vivo generated, embryonic stem cell-derived macrophages (ESDM) improve wound healing in mice. ESDM were tested side by side with bone marrow-derived macrophages (BMDM). Compared to BMDM, ESDM resembled a less inflammatory and more M2-like macrophage subtype as indicated by their reduced responsiveness to lipopolysaccharide, reduced expression of Toll-like receptors, and reduced bacterial phagocytosis. Despite this anti-inflammatory phenotype in cell culture, ESDM prolonged the healing of deep skin wounds even more than BMDM. Healed wounds had more scar formation compared to wounds receiving BMDM or cell-free treatment. Our data indicate that atopical application of ex vivo generated macrophages is not a suitable cell therapy of dermal wounds.
在成年人中，深度受伤的皮肤伤口的修复会导致疤痕组织的形成，而在胚胎中，伤口几乎不会留下疤痕。巨噬细胞是伤口愈合的重要介质，它们分泌细胞因子和组织重塑酶。与由炎症性 M1 巨噬细胞介导的宿主防御不同，伤口愈合和组织修复涉及调节性 M2/M2 样巨噬细胞。胚胎/胎儿巨噬细胞是 M2 样的，这可能促进无疤痕的伤口愈合。在本研究中，我们询问了体外生成的胚胎干细胞衍生的巨噬细胞（ESDM）是否可以改善小鼠的伤口愈合。ESDM 与骨髓衍生的巨噬细胞（BMDM）一起进行了测试。与 BMDM 相比，ESDM 表现出较低的炎症反应和更类似于 M2 样的巨噬细胞亚型，其特征是对脂多糖的反应性降低、Toll 样受体的表达降低以及细菌吞噬作用降低。尽管在细胞培养中表现出抗炎表型，但 ESDM 甚至比 BMDM 更能延长深度皮肤伤口的愈合。与接受 BMDM 或无细胞治疗的伤口相比，愈合的伤口有更多的疤痕形成。我们的数据表明，体外生成的巨噬细胞的局部应用不是皮肤伤口的合适细胞治疗方法。
