Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, 256 Gray's Inn Road, London WC1X 8LD, UK.
J Tissue Eng Regen Med. 2009 Dec;3(8):647-50. doi: 10.1002/term.206.
Fibroblast-epithelium interactions are crucial for successful tissue engineering of skin and oral mucosal equivalents. In this study, we assessed early force generation in organotypic fibroblast-epithelium co-cultures, using normal human keratinocytes (NHK) and HPV16-transformed (UP) cells. During the initial 2 h period, organotypic co-cultures containing both epithelial cell types produced significantly more force than fibroblasts alone (p < 0.05). After 2 h, the epithelial contribution became diminished and did not significantly contribute to intrinsic force generation by fibroblasts, and no differences were observed when using UP vs. NHK. We then measured protease gene expression at the end of the experimental period. Distinct differences were evident in protease expression both between NHK-human skin fibroblast (HSF) vs. UP-HSF co-cultures and compared to fibroblasts alone. We conclude that whilst the very early contractile response of fibroblasts is enhanced by the overlying epithelium, this becomes diminished as the fibroblast response becomes predominant and it does contribute to tissue remodelling via regulation of protease expression.
成纤维细胞-上皮细胞相互作用对于成功进行皮肤和口腔黏膜等同质化组织工程至关重要。在这项研究中，我们使用正常的人角质形成细胞（NHK）和 HPV16 转化（UP）细胞评估了器官型成纤维细胞-上皮细胞共培养物中的早期力产生。在最初的 2 小时内，包含两种上皮细胞类型的器官型共培养物产生的力明显大于单独的成纤维细胞（p<0.05）。2 小时后，上皮细胞的贡献减少，并且对成纤维细胞固有力产生没有显著贡献，并且当使用 UP 与 NHK 时没有观察到差异。然后，我们在实验结束时测量了蛋白酶基因的表达。在 NHK-人皮肤成纤维细胞（HSF）与 UP-HSF 共培养物之间以及与单独的成纤维细胞相比，蛋白酶表达存在明显差异。我们的结论是，尽管成纤维细胞的早期收缩反应受到上层上皮细胞的增强，但随着成纤维细胞反应成为主导，这种增强作用会减弱，并且通过调节蛋白酶表达有助于组织重塑。
