Costea Daniela Elena, Loro Lado Lako, Dimba Elisabeth Anne Okumo, Vintermyr Olav Karsten, Johannessen Anne Christine
Department of Odontology-Oral Pathology and Forensic Odontology, Faculty of Dentistry, University of Bergen, Norway.
J Invest Dermatol. 2003 Dec;121(6):1479-86. doi: 10.1111/j.1523-1747.2003.12616.x.
The connective tissue is known to have a general supportive effect for the development of the overlying epithelium; however, the more specific effects of fibroblasts and the involvement of their product, keratinocyte growth factor, on oral epithelial morphogenesis have not yet been addressed. Therefore, the purpose of this study was to investigate the effects of fibroblasts and keratinocyte growth factor on human oral epithelial morphogenesis in vitro. Reconstituted human oral epithelium was generated from primary human oral keratinocytes and fibroblasts by use of an organotypic cell culture model in a defined medium. Addition of fibroblasts to the collagen biomatrix increased total epithelial thickness from 28.0+/-5.0 microm to 66.1+/-8.6 microm (p=0.028), and basal cell proliferation from 3.6+/-0.7% to 16.6+/-1.1% (p=0.025). Presence of fibroblasts profoundly influenced the pattern of epithelial differentiation, and induced a switch in the pattern of cell death, from a predominance of spontaneous cell death in the basal cell layer (from 4.7+/-0.6% to 1.8+/-0.3%, p=0.029) to a more prevalent cell death due to terminal differentiation in the suprabasal cell layer (from 4.0+/- 0.1% to 5.4+/-0.1%, p=0.034). Keratinocyte growth factor promoted epithelial growth, but did not significantly enhance epithelial differentiation, demonstrating that fibroblasts possess additional mechanisms to keratinocyte growth factor synthesis that can modulate differentiation of reconstituted human oral epithelium.
已知结缔组织对其上方上皮的发育具有普遍的支持作用；然而，成纤维细胞的更具体作用及其产物角质形成细胞生长因子在口腔上皮形态发生中的参与情况尚未得到研究。因此，本研究的目的是在体外研究成纤维细胞和角质形成细胞生长因子对人口腔上皮形态发生的影响。通过在特定培养基中使用器官型细胞培养模型，从原代人口腔角质形成细胞和成纤维细胞生成重组人口腔上皮。向胶原生物基质中添加成纤维细胞可使上皮总厚度从28.0±5.0微米增加到66.1±8.6微米（p = 0.028），基底细胞增殖从3.6±0.7%增加到16.6±1.1%（p = 0.025）。成纤维细胞的存在深刻影响上皮分化模式，并诱导细胞死亡模式的转变，从基底细胞层中主要为自发细胞死亡（从4.7±0.6%降至1.8±0.3%，p = 0.029）转变为由于基底上层细胞终末分化导致的更普遍的细胞死亡（从4.0±0.1%升至5.4±0.1%，p = 0.034）。角质形成细胞生长因子促进上皮生长，但未显著增强上皮分化，这表明成纤维细胞具有角质形成细胞生长因子合成之外的其他机制，可调节重组人口腔上皮的分化。
