Wound Healing Research Group, Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Alberta, Edmonton, Alberta, Canada.
Wound Repair Regen. 2011 Mar-Apr;19(2):274-85. doi: 10.1111/j.1524-475X.2011.00672.x.
Hypertrophic scar (HTS) following thermal injury and other forms of trauma is a dermal fibroproliferative disorder that leads to considerable morbidity. Because of the lack of an ideal animal model, research is difficult. We have established an HTS model that involves transplanting human split-thickness skin graft (STSG) or full-thickness skin graft (FTSG) onto the backs of nude mice. The animals developed raised, firm, and reddish scars 2 months following transplantation. Histology and micromeasurement indicate raised, thickened engrafted skin with STSG and FTSG. In contrast, thickening was not observed with full-thickness rat skin grafts used as controls. Masson's trichrome staining demonstrates increased accumulations of collagen fibrils in the dermis in both scars grafted with STSG and FTSG. Staining cells with toludine blue and an antibody for F4/80 showed an increase in the infiltration of mast cells and macrophages. Quantification of fibrocytes reveals increased fibrocytes. Moreover, STSG grafted skin had significantly more macrophages, mast cells, and fibrocytes than FTSG. Real-time polymerase chain reaction analysis showed significantly elevated mRNA levels for type I collagen, transforming growth factor-β, connective tissue growth factor and heat shock protein 47 in both types of engrafted skin. These data demonstrate that human skin grafted onto nude mice develops red raised and thickened scars having intrinsic properties that closely resemble HTS formation as seen in humans. Interestingly, STSG developed more scar than FTSG. Furthermore, inflammatory cells and bone marrow-derived fibrocytes may play a critical role in HTS development in this animal model.
烧伤和其他形式创伤后的增生性瘢痕（HTS）是一种皮肤纤维增生性疾病，会导致相当大的发病率。由于缺乏理想的动物模型，研究工作较为困难。我们建立了一种 HTS 模型，即将人部分厚度皮肤移植物（STSG）或全厚度皮肤移植物（FTSG）移植到裸鼠背部。移植后 2 个月，动物出现隆起、坚硬和红色瘢痕。组织学和微观测量表明，STSG 和 FTSG 移植后的移植物皮肤隆起、增厚。相比之下，作为对照的全厚度大鼠皮肤移植物未观察到增厚。Masson 三色染色显示，在 STSG 和 FTSG 移植的瘢痕中，真皮中胶原纤维的积累增加。用甲苯胺蓝和 F4/80 抗体对染色细胞进行染色显示，肥大细胞和巨噬细胞浸润增加。纤维细胞的定量显示纤维细胞增加。此外，STSG 移植皮肤的巨噬细胞、肥大细胞和纤维细胞明显多于 FTSG。实时聚合酶链反应分析显示，两种移植皮肤的 I 型胶原、转化生长因子-β、结缔组织生长因子和热休克蛋白 47 的 mRNA 水平显著升高。这些数据表明，移植到裸鼠上的人皮肤会形成红色隆起和增厚的瘢痕，具有与人 HTS 形成非常相似的内在特性。有趣的是，STSG 比 FTSG 形成更多的瘢痕。此外，炎症细胞和骨髓源性纤维细胞可能在该动物模型中的 HTS 发展中发挥关键作用。
