The Important Role of Human Primary Cells and Immortal Cell Lines in Research and Drug Development

Ivan Chen
3 min readMar 10, 2022

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Cell culture research provides valuable supplementary experiments for in vivo research, allowing more controllable manipulation of cell functions and processes. For decades, cell lines have played a key role in scientific progress, but researchers have become more and more cautious in interpreting data generated only from cell lines. Factors such as misidentification and contaminated cell lines have rekindled interest in primary cells.

Many researchers choose to use cell lines because they are usually highly proliferative and easier to culture and transfect. Most cell lines have been cultured for decades and are well adapted to the two-dimensional culture environment. Therefore, they are usually genetically and phenotypically different from their tissue sources and show altered morphology. Unlike cell lines, primary cells are directly separated from tissues and have a limited service life and limited expansion capabilities. On the positive side, primary cells have normal cell morphology and maintain many important markers and functions. in vivo. For example, endothelial cell lines lack various functional markers, while primary endothelial cells retain these key characteristics.

Compared with cell lines, primary cells are extremely sensitive cells and require additional nutrients not included in traditional media. To optimize survival and growth, primary cells perform best in special media tailored for each cell type. For example, endothelial cells and epithelial cells or neurons have very different nutritional requirements and therefore require unique culture media. Traditional cell culture media rely on serum to provide growth factors, hormones, lipids and other uncertain components to support cell growth. However, for primary cells, high serum levels can lead to differentiation or promote the growth of contaminating cells (such as fibroblasts). In addition, serum is also plagued by rising costs and batch-to-batch variability. Formulating special media with little or no serum can avoid these problems, while allowing for greater customization to promote the growth of individual primary cell types. Other approaches, such as seeding primary cells on a more physiologically relevant matrix instead of using synthetic polymers, can significantly improve cell attachment, growth, and purity.

The study of primary cells relies on decades of research using cell lines. Since the beginning of the 20th century, cell lines have provided scientists with an in-depth understanding of the biological processes of human cells. Immortal cell lines have become powerful tools for countless applications, including testing drug metabolism and cytotoxicity, studying gene function, and producing vaccines, antibodies, and biological compounds.

However, even if the experimental results obtained using cell lines can be clearly explained and are consistent with previous studies, please keep in mind that the physiological relevance of these studies may not be very high. There are also restrictions on the operations that researchers can perform on cell lines. In fact, some cells show only marginal similarity with the original primary cells, because continuous passage will cause changes in genotype and phenotype. In the end, changes in the contents of the genome and abnormal expression profiles may be obtained. Cell lines lack key morphological or functional characteristics, so they may not be able to induce relevant biomarkers.

Choose human primary cells or immortal cell lines according to the research goals. In many cases, immortal cell lines provide a very valuable model for preliminary experiments. Then using human primary cells to replicate the key discovery that this increases translation and makes the results more relevant to human physiology.

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