Animal-cell culture media: History, characteristics, and current issues

Animal-cell culture media: History, characteristics, and current issues

Abstract

Background: Cell culture technology has spread prolifically within a century, a variety of culture media has been designed. This review goes through the history, characteristics and current issues of animal-cell culture media.

Methods: A literature search was performed on PubMed and Google Scholar between eighteen eighty and May twenty sixteen using appropriate keywords.

Results: At the dawn of cell culture technology, the major components of media were naturally derived products such as serum. The field then gradually shifted to the use of chemical-based synthetic media because naturally derived ingredients have their disadvantages such as large batch-to-batch variation. Today, industrially important cells can be cultured in synthetic media. Nevertheless, the combinations and concentrations of the components in these media remain to be optimized. In addition, serum-containing media are still in general use in the field of basic research. In the fields of assisted reproductive technologies and regenerative medicine, some of the medium components are naturally derived in nearly all instances.

Conclusions: Further improvements of culture media are desirable, which will certainly contribute to a reduction in the experimental variation, enhance productivity among biopharmaceuticals, improve treatment outcomes of assisted reproductive technologies, and facilitate implementation and popularization of regenerative medicine.

One INTRODUCTION

The influence of cell culture technology on human society has been immeasurable. Progress in biology in recent years, for example, has depended heavily on cell culture technology. In addition, cell culture-based practical technologies have been developed in various areas, including the assessment of the efficacy and toxicity of new drugs, manufacture of vaccines and biopharmaceuticals, and assisted reproductive technology. As the reprogramming of somatic cells became technically feasible recently, researchers around the world are fiercely competing for leadership in the advances of regenerative medicine. In this area likewise, cell culture technology is regarded as a foundation for further development and popularization.

No one probably would argue against the claim that a culture medium is the most important factor in cell culture technology. A medium supports cell survival and proliferation, as well as cellular functions, meaning that the quality of the medium directly affects the research results, the biopharmaceutical production rate, and treatment outcomes of assisted reproductive technology. It is essential, therefore, for investigators who are working with cell cultures to select an appropriate medium that is suitable for their aims. In some cases, researchers should modify a medium themselves. In addition, when facing problems, researchers have to know the properties of the medium in order to identify the cause of any problem with their experiments.

At present, synthetic media can be classified into several groups, based on the type of supplements added; for example, serum-containing media, serum-free media, protein-free media, and chemically defined media. Serum-containing media naturally contain various serum-derived substances, which make the medium composition unclear and whose concentrations can fluctuate from batch to batch. This situation makes the culture results less reproducible and poses a risk of microbial contamination. Serum-containing media, however, can be designed easily and be used effectively for a variety of cell types because serum includes a lot of active substances that are necessary for the survival and growth of animal cells. Serum-free media, in contrast, have a defined composition, resulting in a high reproducibility of results, and the cultivation process can be validated. In addition, target cells can be grown selectively in an intermingled cell population if the culture conditions are configured to benefit them. Among the serum-free media, subgroups of protein-free media (which do not contain any protein at all) and chemically defined media (which do not contain any undefined ingredient) provide additional stability and reproducibility for culture systems, facilitating the identification of the cellular secretions and reducing the risk of microbial contamination. However, the serum-free media are difficult to design: only specific cell types have been cultivated this way to date.

At present, formulations of popular media for cell culture are available commercially. Thus, there are investigators who are using culture media without understanding their details and background, particularly regarding the rationale for their development, the exact ingredients, as well as the cell types that these media are suitable for. This review article briefly describes the history of the development of animal-cell culture media, with comments on the types of media in general use today regarding their characteristics, roles of the medium components, and pitfalls or problems with their use.