Cristóbal Lara, Ortega Miguel A, Asúnsolo Ángel, Romero Beatriz, Álvarez-Mon Melchor, Buján Julia, Maldonado Andrés A, García-Honduvilla Natalio
Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Department of Plastic Surgery, La Zarzuela Hospital, Madrid, Spain.
Histol Histopathol. 2018 Sep;33(9):959-970. doi: 10.14670/HH-11-990. Epub 2018 Apr 17.
Despite advances in regenerative medicine and tissue engineering, human skin substitutes remain a clear goal to achieve. Autografts remain the principal clinical option. The long-term changes in dermis, as well as its response after injuries, are not well known. Research in this field has been hindered by a lack of experimental animal models. This study analyzes the architectural dermal scaffold (collagen and elastin fibers plus fibrillin-microfibrils) changes in a model of human skin pressure ulcers in mice. Immunosuppressed NOD/Scid mice (n=10) were engrafted with human skin of dimensions 4x3 cm. After 60 days as a permanent graft, a pressure ulcer (PU) was created in the human skin using a compression device. Three study groups were established: full-thickness skin graft before (hFTSG) and after applying mechanical pressure (hFTSG-PU). Native human skin was used as control group. Evaluations were conducted with visual and histological assessment. Scaffold components from each group were compared by immunohistochemical staining (tropoelastin, collagen I and III, metalloproteins (MMP), fibulins, and lysil oxidases (LOX) among others). The long-term engrafted skin showed a certain degradative state of dermis scaffold, as noticed by the active expression of MMPs and tropoelastin compared to native skin. However, a great reparative response after pressure ulcer onto the engrafted skin was observed. A significant increase of fibrillin microfibrils components (TGF-β, MAGP-1 and fibrillin-1), and matrix suprastructures of collagen I, III and LOX lead to an active restructuration of dermal tissue. Our human skin model in mice revealed the important role of the dermal scaffold component to reach skin stability and its capability to react to mechanical pressure injuries. These results showed the important role of dermal scaffold to support the histoarchitecture and mechanosensation of the human skin.
尽管再生医学和组织工程取得了进展，但人类皮肤替代物仍是一个明确的有待实现的目标。自体移植仍然是主要的临床选择。真皮的长期变化及其在损伤后的反应尚不清楚。该领域的研究因缺乏实验动物模型而受到阻碍。本研究分析了小鼠人皮肤压疮模型中真皮支架（胶原蛋白、弹性纤维和原纤维微纤维）的结构变化。将免疫抑制的NOD/Scid小鼠（n = 10）移植尺寸为4×3 cm的人皮肤。作为永久移植物60天后，使用压迫装置在人皮肤上造成压疮（PU）。设立了三个研究组：施加机械压力前（hFTSG）和施加机械压力后（hFTSG-PU）的全层皮肤移植。天然人皮肤用作对照组。通过视觉和组织学评估进行评价。通过免疫组织化学染色（原弹性蛋白、I型和III型胶原蛋白、金属蛋白酶（MMP）、纤维连接蛋白和赖氨酰氧化酶（LOX）等）比较每组的支架成分。与天然皮肤相比，长期移植的皮肤显示出真皮支架的一定降解状态，这可通过MMP和原弹性蛋白的活性表达看出。然而，观察到移植皮肤在发生压疮后有很大的修复反应。原纤维微纤维成分（转化生长因子-β、微原纤维相关糖蛋白-1和原纤维蛋白-1）以及I型、III型胶原蛋白和赖氨酰氧化酶的基质超结构显著增加，导致真皮组织的积极重构。我们的小鼠人皮肤模型揭示了真皮支架成分在实现皮肤稳定性及其对机械压力损伤反应能力方面的重要作用。这些结果表明真皮支架在支持人类皮肤组织结构和机械感觉方面的重要作用。
