Polo M, Kim Y J, Kucukcelebi A, Hayward P G, Ko F, Robson M C
University of South Florida, Tampa, USA.
J Surg Res. 1998 Feb 1;74(2):187-95. doi: 10.1006/jsre.1997.5251.
Many aspects related to the biology and the effective therapy of proliferative scars have remained undefined, in part due to a lack of an accurate and reproducible animal model with which to systematically study them. This report describes a new model for investigating the pathophysiology and manipulation of human proliferative scars.
Human proliferative scars (n = 86) were explanted into flaps based on isolated vascular pedicles in congenitally athymic rats. Serial analysis of the structural and functional integrity of the explanted scars was performed by microscopy and by measurement of human procollagen type III peptide (PIIIP) production, human factor VIII immunostaining, and in vitro cellular proliferation.
By these methods, both fibroblastic and epithelial components of explanted scar specimens retained the histologic characteristics of original human scar specimens, for up to 12 months. Over the same duration, scar explants continued to have high levels of human PIIIP, comparable to those found in original surgical specimens. The microvasculature of scar explants demonstrated a double basement membrane, with no staining of human factor VIII in the inner capillary endothelial layer, suggesting that host vessels were growing into ghost vessels of the human donor scar. Human factor VIII staining decreased over time. Fibroblasts cultured from explanted scar demonstrated less aggressive growth characteristics than those from original surgical specimens.
This new model is the first to allow such long-term maintenance and serial evaluation of human proliferative scar on an accessible, isolated vasculature. It may prove useful in further defining the biology and therapy of this widespread pathologic process.
与增生性瘢痕的生物学特性及有效治疗相关的许多方面仍不明确,部分原因是缺乏一种准确且可重复的动物模型来系统地研究它们。本报告描述了一种用于研究人类增生性瘢痕病理生理学及调控的新模型。
将86例人类增生性瘢痕移植到先天性无胸腺大鼠基于孤立血管蒂的皮瓣中。通过显微镜检查以及测量人类III型前胶原肽(PIIIP)生成量、人类因子VIII免疫染色和体外细胞增殖,对移植瘢痕的结构和功能完整性进行系列分析。
通过这些方法,移植瘢痕标本的成纤维细胞和上皮成分在长达12个月的时间内均保留了原始人类瘢痕标本的组织学特征。在相同时间段内,瘢痕移植块的人类PIIIP水平持续较高,与原始手术标本中的水平相当。瘢痕移植块的微血管显示有双层基底膜,内毛细血管内皮层无人类因子VIII染色,提示宿主血管正长入人类供体瘢痕的空壳血管中。人类因子VIII染色随时间减少。从移植瘢痕培养的成纤维细胞显示出比原始手术标本来源的成纤维细胞更弱的生长特性。
这种新模型首次能够在可触及的孤立血管系统上对人类增生性瘢痕进行如此长期的维持和系列评估。它可能有助于进一步明确这一广泛病理过程的生物学特性和治疗方法。