大规模动物细胞培养的研究进展.doc

动物细胞大规模培养技术的研究进展 作者：王珍 指导老师：袁学军 摘要：动物细胞培养作为生化工程学科领域中迅速发展起来的生物技术与化学工程结合的新型学科，无论在基础研究和应用研究方面都越来越受到生物技术界的重视，现已成为生化工程学科主要前沿学科之一。利用动物细胞大规模培养技术可生产多种生物制品，为了提高为提高细胞活力和细胞生长密度, 采用有多种添加成分的无血清培养基培养细胞, 选择既有利于细胞生长又可提高培养细胞密度的微载体和条件温和、易操作、气体交换速度快的生物反应器, 在线监控细胞生存环境和生理活动, 减少培养过程中培养基的抑制因素, 从而 给细胞提供更好的生存环境; 另外通过向细胞中导入抗凋亡基因, 可减缓细胞凋亡的发生, 提高细胞活性和蛋白产量; 此外, 在动物细胞大规模培养过程中, 利用多孔微载体能高效、大量地增殖细胞, 具有良好的应用前景. 关键词: 动物细胞; 培养环境; 生物反应器; 微载体 Research advance in large-scale culture of animal cells Abstract: The technology of animal cell culture is one of the frontiers which combines biotechnology with chemical engineering, and develops rapidly. It plays a more and more important role in both basic and applied research, and is becoming a unique high tech industry and displays tremendous prospects for industrial development. Many biological products were manufactured by means of large- scale culture of animal cells. To increase cell- specific productivity and cell density, serum- free media supplemented with several nutriments were used for cell culture, and microcarriers were chosen in favor of cell growth and high cell density. Biore actors with simple manipulation, good qualification and aeration were adopted. More suitable conditions for cell growth could be given through on- line supervising the environment for cell growth and restraint factors in cell culturing. Furthermore, the anti- apoptosis genes using recombinant DNA technology can increase cell viability and productivity. Porous microcarriers was emphasized in large- scale culture of animal cells. Keywords: animal cell; culture environment; bioreactor; microcarrier search advance in large-scale culture of animal cells. 一、细胞培养技术概述 动物细胞培养开始于本世纪初,1962年, 其规模开始扩大, 发展至今已成为生物、医学研究和应用中广泛采用的技术方法, 利用动物细胞培养生产具有重要医用价值的酶、生长因子、疫苗和单抗等, 已成为医药生物高技术产业的重要部分[1 ]，利用动物细胞培养技术生产的生物制品已占世界生物高技术产品市场份额的50% [2 ]，大量资料表明, 生物技术药物是当前新药开发的重要领域, 生物技术制药工业是下一个10 年制药工业的重要新门类, 期间将有数百种生物技术新药上市[3 ]，美国最新预测几种畅销基因工程药物2000 年全球销售额EPO 大于30 亿美元, G2CSF 大于20 亿美元, HGH、IFN、U K 均大于10 亿美元, 胰岛素和