Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, 127 Chanle West Road, Xi'an, 710032, Shaanxi Province, China.
J Transl Med. 2019 Jan 21;17(1):36. doi: 10.1186/s12967-019-1780-z.
Tissue expansion is a procedure that promotes skin regeneration by mechanical stretch. During the stress and relaxation cycle, the skin undergoes a repeated microtrauma which triggers an immune response leading to the recruitment of macrophages to repair the damaged tissue. Macrophages have been found to be necessary for tissue repair and wound healing, but their effects on skin regeneration during mechanical stretch remain unclear.
The dynamic changes of macrophages in the rat skin tissues undergoing expansion were quantitatively determined by immunohistochemistry staining. The area of the expanded skin, skin thickness, dermal collagen density, cell proliferation and tissue vascularization were examined to determine the effects of macrophages on the expanding skin. The phenotypes of macrophages and the growth factors related to skin regeneration were also examined to evaluate the underlying mechanisms for the involvement of macrophages in skin regeneration. As a comparison, the tissue samples of expanding skin in which the macrophages were depleted by topically utilizing clodronate liposomes were also evaluated.
The number of skin macrophages in skin maintained in the high level during the skin expansion compared to non-expanded skin. We found that a switch from an M1- to M2-dominant response during tissue expansion. After the macrophages were depleted, the skin regeneration was inhibited, as evidenced by a smaller expansion area, thinner skin layers and decreased cell proliferation rate, collagen synthesis and, skin vascularization. The secretion of epidermal growth factor (EGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) were decreased when macrophages were depleted.
Our findings suggest that macrophages are necessary for skin regeneration during tissue expansion. Modulating inflammation may provide a key therapeutic strategy to promote skin growth under mechanical strain.
组织扩张是一种通过机械拉伸促进皮肤再生的程序。在应力和松弛循环过程中，皮肤会经历反复的微创伤，从而引发免疫反应，导致巨噬细胞募集以修复受损组织。已经发现巨噬细胞对于组织修复和伤口愈合是必要的，但它们在机械拉伸过程中对皮肤再生的影响尚不清楚。
通过免疫组织化学染色定量测定接受扩张的大鼠皮肤组织中巨噬细胞的动态变化。检查扩张皮肤的面积、皮肤厚度、真皮胶原密度、细胞增殖和组织血管化，以确定巨噬细胞对扩张皮肤的影响。还检查了巨噬细胞的表型和与皮肤再生相关的生长因子，以评估巨噬细胞参与皮肤再生的潜在机制。作为比较，还评估了通过局部应用氯膦酸盐脂质体耗尽巨噬细胞的扩张皮肤组织样本。
与非扩张皮肤相比，在皮肤扩张过程中保持高水平的皮肤巨噬细胞数量。我们发现，在组织扩张过程中，从 M1 型向 M2 型优势反应的转变。在耗尽巨噬细胞后，皮肤再生受到抑制，表现为扩张面积较小、皮肤层较薄、细胞增殖率、胶原合成和皮肤血管化降低。当耗尽巨噬细胞时，表皮生长因子 (EGF)、成纤维细胞生长因子 (FGF) 和血管内皮生长因子 (VEGF) 的分泌减少。
我们的研究结果表明，巨噬细胞是组织扩张过程中皮肤再生所必需的。调节炎症可能为在机械应变下促进皮肤生长提供关键的治疗策略。
