Laplante A F, Germain L, Auger F A, Moulin V
Laboratoire d'organogénèse expérimentale (LOEX), Hôpital Saint-Sacrement du CHA de Québec and Surgery Department, Laval University, Québec, Canada.
FASEB J. 2001 Nov;15(13):2377-89. doi: 10.1096/fj.01-0250com.
Wound closure of epithelial tissues must occur efficiently to restore rapidly their barrier function. We have developed a tissue-engineered wound-healing model composed of human skin keratinocytes and fibroblasts to better understand the mechanisms of reepithelialization. It allowed us to quantify the reepithelialization rate, which was significantly accelerated in the presence of fibrin or platelet-rich plasma. The reepithelialization of these 6 mm excisional wounds required the contribution of keratinocyte proliferation, migration, stratification, and differentiation. The epidermis regenerated progressively from the surrounding wound margins. After 3 days, the neoepidermis showed a complete spectrum of changes. Near the wound margin, the differentiation of the neoepidermis (keratins 1/10, filaggrin, and loricrin) and regeneration of the dermoepidermal junction (laminin 5 and collagen IV) were more advanced than toward the wound center, where the proliferative index was significantly increased. The spatial distribution of keratinocytes distinguished by particular features suggests two complementary mechanisms of reepithelialization: 1) the passive displacement of the superficial layers near the wound margin that would rapidly regenerate a barrier function and 2) the crawling of keratinocytes over each other at the tip of the progressing neoepidermis. Therefore, this study brings a new perspective to long-standing questions concerning wound reepithelialization.
上皮组织的伤口闭合必须高效进行，以便迅速恢复其屏障功能。我们构建了一种由人皮肤角质形成细胞和成纤维细胞组成的组织工程化伤口愈合模型，以更好地理解再上皮化的机制。这使我们能够量化再上皮化速率，在存在纤维蛋白或富含血小板血浆的情况下，该速率显著加快。这些6毫米切除伤口的再上皮化需要角质形成细胞增殖、迁移、分层和分化的参与。表皮从周围伤口边缘逐渐再生。3天后，新表皮呈现出一系列完整的变化。在伤口边缘附近，新表皮的分化（角蛋白1/10、丝聚蛋白和兜甲蛋白）以及真皮表皮交界处（层粘连蛋白5和IV型胶原）的再生比朝着伤口中心更明显，而伤口中心的增殖指数显著增加。以特定特征区分的角质形成细胞的空间分布提示了两种互补的再上皮化机制：1）伤口边缘附近表层的被动移位，这将迅速再生屏障功能；2）角质形成细胞在进展中的新表皮尖端相互爬行。因此，本研究为有关伤口再上皮化的长期问题带来了新的视角。
