ERYTHROPOIETIN PRODUCTION IN CHINESE HAMSTER OVARY: THE THREADS AND KNOTS OF PROPER CULTURE ENVIRONMENTAL FACTORS IMPROVED GLYCOSYLATION , FUNCTION AND PRODUCTIVITY

Erythropoietin (EPO) is a glycoprotein that regulates erythropoiesis under hypoxic conditions through the pro liferation and differentiation of red blood cell precursors. It is used in the treatment of anemia caused by chronic renal failure and cancer therapies. EPO is commercially produced in Chinese Hamster Ovary (CHO) cells in industrial scale bioreactors. Limi tations in EPO production protocols include low yields, high costs and insufficient glycosylation. Adjustments in mechanical parameters such as temperature reduction and carbon dioxide concentrations have been shown to increase both quantity and quality of EPO production. As cells use up glucose, acidifying lactate is produced as waste which adversely affects glycosylation and quantity of EPO. The accumulation of lactate shortens the culture span which affects the viability of production systems. This has s hown to be remedied through the addition of lactate salts such as sodium lactate which neutralize acidity and decrease specific growth rate. Additionally, medium protecting additives in stir - tank bioreactors can have an effect on EPO quality and quantity. The use of environmental friendly, non - toxic additives like poly - γ - glutamic acid can help protect cells during culture by minimizing sheer stress resulting in better quality EPO than that produced using Pluronics that have been shown to inhibit DNA synthes is. Not only the correct choice of the combination profile - temperature, pH, lactate salts and sheer protecting additives - is helpful; but also the appropriate alternating time cycle for each factor in the correct profile is also as much important.