Department of Burns and Plastic Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Department of Emergency, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8110-8122. doi: 10.3892/mmr.2017.7672. Epub 2017 Sep 29.
The regenerative repair of deep‑degree (second degree) burned skin remains a notable challenge in the treatment of burn injury, despite improvements being made with regards to treatment modality and the emergence of novel therapies. Fetal skin constitutes an attractive target for investigating scarless healing of burned skin. To investigate the inflammatory response during scarless healing of burned fetal skin, the present study developed a nude mouse model, which was implanted with normal human fetal skin and burned fetal skin. Subsequently, human peripheral blood mononuclear cells (PBMCs) were used to treat the nude mouse model carrying the burned fetal skin. The expression levels of matrix metalloproteinase (MMP)‑9 and tissue inhibitor of metalloproteinases (TIMP)‑1 were investigated during this process. In the present study, fetal skin was subcutaneously implanted into the nude mice to establish the murine model. Hematoxylin and eosin staining was used to detect alterations in the skin during the development of fetal skin and during the healing process of deep‑degree burned fetal skin. The expression levels of MMP‑9 and TIMP‑1 were determined using immunochemical staining, and their staining intensity was evaluated by mean optical density. The results demonstrated that fetal skin subcutaneously implanted into the dorsal skin flap of nude mice developed similarly to the normal growth process in the womb. In addition, the scarless healing process was clearly observed in the mice carrying the burned fetal skin. A total of 2 weeks was required to complete scarless healing. Following treatment with PBMCs, the burned fetal skin generated inflammatory factors and enhanced the inflammatory response, which consequently resulted in a reduction in the speed of healing and in the formation of scars. Therefore, exogenous PBMCs may alter the lowered immune response environment, which is required for scarless healing, resulting in scar formation. In conclusion, the present study indicated that the involvement of inflammatory cells is important during the healing process of deep‑degree burned skin, and MMP‑9 and TIMP‑1 may serve important roles in the process of scar formation.
深度烧伤(二度)皮肤的再生修复仍然是烧伤治疗中的一个显著挑战,尽管在治疗方式上有所改进,并且出现了新的治疗方法。胎儿皮肤是研究无瘢痕烧伤皮肤愈合的理想目标。为了研究无瘢痕愈合烧伤胎儿皮肤的炎症反应,本研究建立了裸鼠模型,将正常胎儿皮肤和烧伤胎儿皮肤植入裸鼠。随后,用人外周血单核细胞(PBMC)治疗携带烧伤胎儿皮肤的裸鼠模型。在此过程中,研究了基质金属蛋白酶(MMP)-9 和金属蛋白酶组织抑制剂(TIMP)-1 的表达水平。本研究将胎儿皮肤皮下植入裸鼠,建立了鼠模型。苏木精-伊红染色用于检测胎儿皮肤发育过程中和深度烧伤胎儿皮肤愈合过程中皮肤的变化。免疫化学染色法检测 MMP-9 和 TIMP-1 的表达水平,并通过平均光密度评估其染色强度。结果表明,皮下植入裸鼠背部皮瓣的胎儿皮肤的发育过程与子宫内的正常生长过程相似。此外,携带烧伤胎儿皮肤的小鼠中明显观察到无瘢痕愈合过程。完全无瘢痕愈合需要 2 周时间。经 PBMC 治疗后,烧伤胎儿皮肤产生炎症因子,增强炎症反应,导致愈合速度减慢,形成瘢痕。因此,外源性 PBMC 可能改变无瘢痕愈合所需的降低的免疫反应环境,导致瘢痕形成。总之,本研究表明,炎症细胞的参与对深度烧伤皮肤的愈合过程很重要,MMP-9 和 TIMP-1 在瘢痕形成过程中可能发挥重要作用。