- Immortalized cell lines are populations of cells that have acquired the ability to proliferate indefinitely under specific culture conditions, making them indispensable tools in biomedical and life sciences research. These cells originate from normal tissues, tumors, or stem cells, and are modified—either spontaneously or deliberately—to bypass normal cellular senescence and apoptosis.
- Under standard circumstances, somatic cells possess a finite replicative capacity, typically governed by the Hayflick limit, which is largely determined by telomere shortening. In immortalized cells, mechanisms that extend telomere length or override cell cycle checkpoints allow for continuous division and long-term propagation in vitro.
- Immortalization can occur through natural processes, such as in cancer cells, which inherently evade growth-inhibitory signals and resist programmed cell death.
- The HeLa cell line, derived from cervical cancer cells of Henrietta Lacks in 1951, was the first human cell line to be cultured successfully and remains widely used today.
- Alternatively, immortalization can be artificially induced in primary cells using various molecular techniques.
- One common method involves the introduction of viral genes, such as the simian virus 40 (SV40) large T antigen, which inactivates tumor suppressor proteins p53 and Rb, allowing cells to bypass growth arrest.
- Another widely used approach is the transfection of the human telomerase reverse transcriptase (hTERT) gene, which prevents telomere shortening, thereby promoting replicative immortality without necessarily transforming the cell into a cancerous phenotype.
- Immortalized cell lines offer numerous advantages. They provide a renewable, consistent, and easily maintainable supply of homogeneous cells, facilitating experimental reproducibility. These lines are extensively used for investigating basic cellular processes—such as cell signaling, gene regulation, differentiation, and apoptosis—as well as for high-throughput screening in drug discovery, vaccine development, and toxicology testing. Additionally, they are frequently employed in recombinant protein production, especially in pharmaceutical biotechnology. For example, Chinese Hamster Ovary (CHO) cells are the industry standard for producing monoclonal antibodies and therapeutic proteins due to their adaptability and favorable post-translational modification capabilities.
- However, immortalized cell lines are not without limitations. The process of immortalization often alters cellular physiology, resulting in changes to gene expression profiles, karyotype instability, and loss of tissue-specific characteristics. Over extended culture periods, immortalized lines may accumulate mutations, leading to genetic drift and potential divergence from the original cell type. This can compromise the biological relevance of the data generated from these models. Moreover, because many immortalized lines are derived from tumors or are artificially transformed, they may not accurately reflect the behavior of normal primary cells in vivo.
- Given these limitations, the scientific community increasingly emphasizes the importance of validating findings from immortalized cell lines using more physiologically relevant models, such as primary cells, induced pluripotent stem cells (iPSCs), 3D organoids, or animal models. Nonetheless, immortalized cell lines continue to be powerful and practical models that have advanced our understanding of human biology, disease mechanisms, and therapeutic development. Proper characterization, authentication, and controlled use of these lines remain essential to ensuring the reliability and translational value of the research they support.
