Development of polymer medicines production system ulilzing polarized epithelial culturing method.

极化上皮细胞的特征在于具有两个质膜结构域，即顶侧结构域和基底侧结构域，具有不同的结构和功能。上皮细胞的极性不仅限于质膜成分，而且分泌蛋白也以极化方式释放。MDCK细胞是一种典型的犬肾上皮细胞系，已被广泛用于研究膜脂和蛋白质载体转运的分子机制。促红细胞生成素（Epo）是红细胞生成的主要生理调节因子，通过刺激红系前体细胞的增殖和分化而发挥作用。我们发现重组人Epo优先从MDCK细胞的顶端结构域分泌。利用这种极化分泌，我们已经开发了一个中试系统，在工业规模生产Epo。我们收集了设计中空纤维系统的基本信息，其中Epo将在纤维内部或外部释放。

Polarized epithelial cells are characterized by two plasma membrane domains, apical and basolateral domains, having different structure and functions. The polarity of epithelial cells is not only restricted to plasma membrane components but secretory proteins are also released in a polarized fashion. MDCK cells are a typical epithelial cell line derived from dog kidney and have been widely used to investigate molecular mechanism of vectorial transport of membrane lipids and proteins. Erythropoietin (Epo) is a major physiological regulator of erythropoiesis by stimulating proliferation and differentiation of erythroid precursor cells. We here found that recombinant human Epo is preferentially secreted from the apical domain of MDCK cells. Taking advantage of this polarized secretion, we have developed a pilot system of producing Epo in industrial scale. We have collected basic information of deigning hollow-fiber system in which Epo will be released either inside or outside of the fiber.