Mammalian Cell Culture in Medical Research

Mammalian cell culture refers to cells that are isolated from the body of a mammal and are placed into an artificial medium (in vitro) which promotes their growth. Special skills and methods of preservation are needed to maintain the viability, structure and function of the cells in culture. The first techniques for the preparation of cell cultures were developed by R. Harrison in the early twentieth century (Nema and Khare, 2012). The first mammalian cell culture was discovered by Earle in 1948 as he established the first cell line ("L" cell line) derived from subcutaneous mouse tissue (Marquis, 1997).

Nowadays, the cultivation of animal and human cells in vitro is widely used both in practical and scientific research. The future of biology and medicine is directly linked to the development of cell cultures; therefore, it is impossible to imagine modern laboratories without them. The mammalian cell cultures are a significant tool for scientists to produce and test new drugs, vaccines, they are widely used in gene therapy, cancer research, stem cell biology, recombinant protein production, etc.

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(Nema and Khare, 2012).

The first important application of human cells in vitro was in the production of the Salk vaccine against polio infection by Doctor Jonas Salk. Firstly, polio virus was grown on a human kidney cell culture, then, it was treated with formalin resulting in an immunogenic preparation – a vaccine (Marquis, 1997). The discovery of the Salk vaccine played a vital role in saving the lives of many people, mostly children. At the present time, the mammalian cells in vitro are extensively used for the manufacture of new vaccines.

For example, the vaccines against influenza virus which kills lots of people worldwide can be produced using human embryonic retinal cells, kidney cells of Madin Darby canine, human embryo or monkey that are grown in vitro (Milian and Kamen, 2015).

One of the latest developments of cell culture technologies are three-dimensional cultures which give many opportunities: they accurately imitate the shape of cells and their features that are closer to in vivo microenvironment. The 3-D models of mammalian cell cultures are specifically important for cancer research and drug discovery as they mimic the tumour microenvironment. They have been used to study the behaviour of cancer cells, their response to various growth factors, chemotherapy and anti-tumour drugs (Doglai et al, 2017).

Moreover, there are also specific 3D culture conditions that allow the cells to grow over long periods of time, so they are useful for various research purposes. For instance, a recent study describes a long-term 3D culture system which allowed the mature human and murine hepatocytes to expand and proliferate in a period of 6 months. The expansion of these cells resulted in the formation of functional ‘hepatocyte organoids' which were successfully engrafted as single cells into the damaged liver tissue of a mouse by splenic injection; the transplanted cells were able to grow and function normally within the liver (Hu et al, 2018). Therefore, the long-term in-vitro cultivation of mammalian hepatocytes plays a crucial role in regenerative therapy of the liver, in addition, as the authors of this study mention (2018: p. 1603), it can also be used to study the malaria, viral hepatitis and other liver diseases.

In recent years, biopharmaceuticals have become the fastest developing industry on the market as they are the most effective clinical tools to combat diseases. Apart from vaccines, biopharmaceutical products also include clinical reagents and drugs; most of them are recombinant proteins of organic origin, obtained mainly from microorganisms and mammalian cells.

Among the latest 18 recombinant drugs, 12 are generated using mammalian expression systems thus, mammalian cells are the dominant sources for biopharmaceutical production. This is due to the fact that mammalian cells synthesize proteins that resemble the natural human proteins both in structure and function. Most of the popular biopharmaceuticals have been manufactured using Chinese hamster ovary (CHO) cells, murine myeloma lymphoblastoid-like (NS0 and Sp2/0-Ag14) cells and Human Embryonic Kidney 293 (HEK 293) cells.