Inferences of Carbon Dioxide in Present-Day Cell Culture Systems: An Unacknowledged Problem and Perspectives

The impact of cell culture technology has been immense in the field of research and pharmaceutical sciences. Suitable environmental conditions are paramount need in order to maintain the cell line in an in-vitro condition. Since the biological processes are highly susceptible to acid-base chemistry, variations among the factors will have a severe effect on cellular integrity that often leads to hypercapnia and senescence of the cells. pH regulation in the cell culture environment is a fundamental biological phenomenon of great significance for the growth and metabolism of cells. This review focuses on the implications of the two critical factors carbon dioxide (CO2), pH, and their correlated effects in the mammalian culture system. Bicarbonate buffer plays a vital role in maintaining homeostasis as dissolved CO2 hydration occurs in bicarbonate (HCO3-) and H+ equilibriums. If pH is not controlled, inhibition of CO2 causes acidification in the medium. In contrast, if pH is not regulated by integrating essential requirements, the equilibrium reaction shifts to the right towards the hydrogen ions that maintains the balance. Despite a few literatures exhibiting the role of carbon dioxide in cell culture, the present review distinguishes from them by showing the effects of CO2 in the in-vitro environment in maintaining the pH balance and cellular integrity. Thus, ensuring the proper mechanism of the utilization of CO2 and pH in the cell culture system will undoubtedly lead to the exploration of enormous concepts in the present crucial study.