Kobayashi Ken, Nomoto Yukio, Suzuki Teruhisa, Tada Yasuhiro, Miyake Masao, Hazama Akihiro, Kanemaru Shinichi, Nakamura Tatsuo, Omori Koichi
Department of Otolaryngology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Tissue Eng. 2006 Sep;12(9):2619-28. doi: 10.1089/ten.2006.12.2619.
Several artificial grafts for covering deficient trachea have been produced through tissue engineering. Recently, our group clinically used an artificial trachea made from collagen sponge for patients with noncircumferential tracheal resection. However, the slowness of epithelial regeneration on the surface of the artificial trachea was confirmed as one particular problem. In this study, we co-cultured tracheal epithelial cells with fibroblasts and examined effects of fibroblasts on epithelial regeneration in vitro. Fibroblasts activated epithelial cell proliferation and migration. In co-culture with fibroblasts, epithelial cells reconstructed pseudostratified epithelium, which was composed of ciliated, goblet, and basal cells. Furthermore, a basement membrane was reconstructed between epithelial cells and fibroblasts, and integrin beta4 was also observed there. Fibroblasts rapidly increased mucin secretion by epithelial cells. These results indicate that stimulatory effects of fibroblasts on epithelial cell migration, proliferation, and differentiation would reduce the time required for covering of epithelial cells on the defect of luminal surface and hasten regeneration of morphologically and functionally normalized epithelium involving the reconstruction of basement membrane.
通过组织工程已经制备了几种用于覆盖气管缺损的人工移植物。最近,我们的团队在临床上将由胶原海绵制成的人工气管用于非环形气管切除的患者。然而,人工气管表面上皮再生缓慢被确认为一个特殊问题。在本研究中,我们将气管上皮细胞与成纤维细胞共培养,并在体外研究了成纤维细胞对上皮再生的影响。成纤维细胞激活了上皮细胞的增殖和迁移。与成纤维细胞共培养时,上皮细胞重建了由纤毛细胞、杯状细胞和基底细胞组成的假复层上皮。此外,上皮细胞和成纤维细胞之间重建了基底膜,并且在那里也观察到了整合素β4。成纤维细胞迅速增加了上皮细胞的粘蛋白分泌。这些结果表明,成纤维细胞对上皮细胞迁移、增殖和分化的刺激作用将减少覆盖管腔表面缺损处上皮细胞所需的时间,并加速涉及基底膜重建的形态和功能正常化上皮的再生。