Bayne C W, Donnelly F, Chapman K, Bollina P, Buck C, Habib F
University Department of Surgery, Western General Hospital, Edinburgh.
J Clin Endocrinol Metab. 1998 Jan;83(1):206-13. doi: 10.1210/jcem.83.1.4486.
We have developed a coculture system for primary fibroblast and epithelial cells derived from benign prostatic hyperplasia (BPH) that retained many of the characteristics of the intact human prostate. In contrast to separately cultured prostate fibroblast and epithelial cells, cocultures of fibroblasts and epithelial cells maintained messenger ribonucleic acid expression and functional activity for both isoenzymes of 5 alpha-reductase (type I and type II) as well as maintained expression of androgen receptors and prostate-specific antigen. Furthermore, levels of prostate-specific antigen secreted by cocultured epithelial cells were increased by treatment with androgens, mimicking the situation in the human gland. This contrasted with conventionally cultured fibroblasts or epithelial cells, which failed to express 50 alpha-reductase type II and rapidly lost expression of androgen receptors and androgen sensitivity upon being placed into culture. Electron microscopy demonstrated intracellular structures indicative of the differentiated state of the cocultured cell types, including round nuclei, tonofibrils, and microvilli in epithelial cells and elongated nuclei; large amounts of Golgi and cilia; along with immature collagen fibers in fibroblasts. The present study demonstrates that the coculture model reflects more closely the in vivo system for human BPH and is thus a far more suitable model for investigating the molecular and cellular events that underlie BPH than current in vitro systems.
我们已经开发出一种用于良性前列腺增生（BPH）来源的原代成纤维细胞和上皮细胞的共培养系统，该系统保留了完整人类前列腺的许多特征。与单独培养的前列腺成纤维细胞和上皮细胞不同，成纤维细胞和上皮细胞的共培养维持了5α-还原酶两种同工酶（I型和II型）的信使核糖核酸表达和功能活性，同时维持了雄激素受体和前列腺特异性抗原的表达。此外，共培养的上皮细胞分泌的前列腺特异性抗原水平通过雄激素处理而增加，这模拟了人体腺体中的情况。这与传统培养的成纤维细胞或上皮细胞形成对比，后者不表达II型5α-还原酶，并且在培养后迅速丧失雄激素受体表达和雄激素敏感性。电子显微镜显示细胞内结构表明共培养细胞类型的分化状态，包括上皮细胞中的圆形细胞核、张力原纤维和微绒毛，以及细长的细胞核；大量的高尔基体和纤毛；以及成纤维细胞中未成熟的胶原纤维。本研究表明，共培养模型更紧密地反映了人类BPH的体内系统，因此是一种比当前体外系统更适合研究BPH潜在分子和细胞事件的模型。
