Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Singapore Management University, Singapore, Singapore.
Cell Rep. 2024 Oct 22;43(10):114742. doi: 10.1016/j.celrep.2024.114742. Epub 2024 Sep 21.
Mammals typically heal with fibrotic scars, and treatments to regenerate human skin and hair without a scar remain elusive. We discovered that mice lacking C-X-C motif chemokine receptor 2 (CXCR2 knockout [KO]) displayed robust and complete tissue regeneration across three different injury models: skin, hair follicle, and cartilage. Remarkably, wild-type mice receiving plasma from CXCR2 KO mice through parabiosis or injections healed wounds scarlessly. A comparison of circulating proteins using multiplex ELISA revealed a 24-fold higher plasma level of granulocyte colony stimulating factor (G-CSF) in CXCR2 KO blood. Local injections of G-CSF into wild-type (WT) mouse wound beds reduced scar formation and increased scarless tissue regeneration. G-CSF directly polarized macrophages into an anti-inflammatory phenotype, and both CXCR2 KO and G-CSF-treated mice recruited more anti-inflammatory macrophages into injured areas. Modulating macrophage activation states at early time points after injury promotes scarless tissue regeneration and may offer a therapeutic approach to improve healing of human skin wounds.
哺乳动物通常会形成纤维疤痕愈合，而能再生无疤痕的人类皮肤和毛发的治疗方法仍难以捉摸。我们发现，缺乏 C-X-C 基序趋化因子受体 2（CXCR2 敲除 [KO]）的小鼠在三种不同的损伤模型中表现出强大而完全的组织再生：皮肤、毛囊和软骨。值得注意的是，通过联体共生或注射将 CXCR2 KO 小鼠的血浆给予野生型（WT）小鼠后，伤口可无痕愈合。使用多重 ELISA 比较循环蛋白显示，CXCR2 KO 血液中的粒细胞集落刺激因子（G-CSF）水平高 24 倍。将 G-CSF 局部注射到 WT 小鼠的伤口床中可减少疤痕形成并增加无疤痕组织再生。G-CSF 直接将巨噬细胞极化为抗炎表型，并且 CXCR2 KO 和 G-CSF 治疗的小鼠将更多抗炎性巨噬细胞募集到受损区域。在损伤后早期调节巨噬细胞的激活状态可促进无疤痕组织再生，并可能为改善人类皮肤伤口愈合提供一种治疗方法。
