Cell lines are a cornerstone of modern biomedical science, enabling researchers to study cellular processes in controlled environments. Unlike primary cells, which have a finite lifespan and are often difficult to obtain, immortalised lines can proliferate indefinitely, offering consistency and reproducibility across experiments. This characteristic makes them invaluable for investigating human diseases, drug development, toxicology, and molecular biology.
Over time, certain cell lines have risen to prominence because of their versatility, ease of handling, and broad applications. Each one provides a different perspective on cellular physiology, cancer biology, immune responses, or organ-specific functions. Understanding their background and purpose not only guides proper use but also ensures scientific findings are interpreted with the correct context.
The following sections explore ten influential cell lines that have played defining roles in both academic and industrial research, tracing their origins, primary applications, and scientific contributions.
The Enduring Significance of HeLa Cells
HeLa cells were the first immortalised human cell line, derived from cervical carcinoma tissue taken from Henrietta Lacks in 1951. Their ability to divide indefinitely transformed cell biology, as prior to their development, most cultures died after only a few divisions.
HeLa cells have been involved in countless scientific milestones. They were essential for testing the first polio vaccines, contributing to the eradication of a global epidemic. They have also been used in mapping the human genome, advancing cancer biology, and exploring how viruses hijack human cells.
Their advantages include fast growth, adaptability to various culture conditions, and resilience under experimental manipulation. Researchers utilise them to study DNA replication, tumour suppressor genes, oncogenes, and chromosomal abnormalities. However, their highly mutated genome and aggressive proliferation mean results often require validation in additional models. Furthermore, their history sparked discussions around bioethics, consent, and patient rights, influencing modern regulations on biological sample use.
The Adaptability of HEK293
The development of HEK293 cells in the 1970s provided researchers with an adaptable and transfection-friendly line. Derived from embryonic kidney tissue, they became one of the most widely used human lines in molecular biology. Their high efficiency for DNA uptake and protein expression makes them a preferred host for recombinant protein and viral vector production.
HEK293 cells underpin several research areas:
- Gene therapy: They are the backbone of adenoviral and lentiviral vector production, widely used in clinical trials.
- Pharmacology: HEK293 derivatives are used to test receptor binding, ion channel activity, and intracellular signalling.
- Structural biology: Large amounts of proteins can be expressed in HEK293 cells for crystallographic studies.
Despite their kidney origin, these cells exhibit properties closer to neuronal phenotypes, which can influence interpretation in some contexts. Nonetheless, their reproducibility, scalability, and versatility ensure their continued role in cutting-edge biotechnology.
CHO Cells: A Biopharmaceutical Workhorse
CHO cells, originating from Chinese hamster ovary tissue, are not commonly used to study disease but dominate the field of therapeutic protein production. They have become the gold standard in the biopharmaceutical industry because they are safe, adaptable, and capable of human-like glycosylation.
Their impact includes:
- Monoclonal antibodies: Most therapeutic antibodies, including those for autoimmune diseases and cancers, are produced in CHO lines.
- Recombinant proteins: Enzymes, clotting factors, and hormones are manufactured at industrial scale.
- Flexibility: CHO cells adapt well to serum-free media, reducing contamination risks and simplifying downstream purification.
The adaptability of CHO cells to large-scale bioreactors makes them indispensable in bringing laboratory discoveries to clinical therapies. While they are not typically used in disease modelling, their role in translating molecular research into treatments underscores their value.
SH-SY5Y in Neurodegenerative Research
The neuroblastoma-derived SH-SY5Y cell line has become one of the most widely used models for studying neuronal function and pathology. Under specific culture conditions, these cells can differentiate into neuron-like phenotypes, expressing neurotransmitter receptors and forming axonal projections.
They are particularly useful for:
- Neurodegeneration: Studies on Parkinson’s, Alzheimer’s, and Huntington’s diseases rely heavily on SH-SY5Y cells to mimic neuronal behaviour.
- Drug neurotoxicity: Compounds can be tested for their impact on synaptic function and viability.
- Cellular signalling: These cells allow in-depth analysis of neurotransmitter systems and calcium signalling pathways.
Their tumour origin limits their direct comparability to primary neurons, yet their adaptability, affordability, and responsiveness keep them central to neuroscience laboratories worldwide.
MCF7 and Hormone-Responsive Breast Cancer
Breast cancer research has long depended on MCF7 cells, derived in 1970 from metastatic breast adenocarcinoma. These cells express oestrogen receptors, making them highly relevant for investigating hormone-responsive tumours.
Researchers employ MCF7 cells to:
- Examine mechanisms of endocrine therapies such as tamoxifen.
- Study apoptosis, proliferation, and drug resistance in oestrogen-positive cancers.
- Test chemotherapeutic compounds targeting breast cancer pathways.
While highly representative of ER-positive breast cancer, MCF7 cells do not reflect all subtypes, including triple-negative and HER2-positive forms. Nevertheless, they remain a benchmark in oncology, particularly in hormonal therapy research.
THP1: A Window into the Immune System
The monocytic leukaemia-derived THP1 line provides researchers with a versatile model of innate immunity. THP1 cells can differentiate into macrophage-like cells, making them especially useful for studying inflammation and host–pathogen interactions.
Applications include:
- Analysing Toll-like receptor signalling and cytokine production.
- Testing immune responses to nanoparticles, toxins, and pharmaceuticals.
- Investigating pathogen recognition and HIV replication in myeloid cells.
While THP1 cells cannot mimic the full diversity of human immune responses, they offer a reproducible and accessible alternative to primary monocytes, bridging gaps in immunological research.
A2780 and Advances in Ovarian Cancer Treatment
A2780 cells, derived from ovarian carcinoma, are frequently used to study chemotherapy sensitivity, particularly to platinum-based drugs such as cisplatin. They provide insight into mechanisms of drug resistance, which is a major obstacle in clinical oncology.
Their applications span:
- Identifying biomarkers for platinum resistance.
- Testing drug combinations that enhance efficacy or reverse resistance.
- Exploring DNA damage repair pathways critical to ovarian tumour survival.
Although in vitro models cannot perfectly replicate tumour heterogeneity, A2780 cells remain vital for guiding experimental therapies and designing clinical strategies.
HL-60 and Leukaemia Differentiation Studies
Promyelocytic HL-60 cells, established in 1977, offer a unique opportunity to investigate haematopoietic differentiation. They can be induced to form either granulocytic or monocytic lineages depending on experimental treatment.
This versatility enables research into:
- Oncogenesis and leukaemia development.
- Differentiation-based therapies, such as retinoic acid treatment.
- Toxicological studies examining drug effects on blood cells.
HL-60 cells have informed both the understanding of leukaemia biology and the development of novel therapeutic strategies targeting myeloid malignancies.
Caco-2 and the Intestinal Barrier
The colon adenocarcinoma-derived Caco-2 line is indispensable for modelling intestinal absorption. When cultured for extended periods, Caco-2 cells differentiate into enterocyte-like cells with brush-border membranes and tight junctions.
They are particularly important for:
- Drug permeability studies to predict oral bioavailability.
- Nutrient absorption modelling in nutritional science.
- Investigating gut epithelial responses to microbiota and toxins.
Regulatory agencies often accept Caco-2 assays as a standard for preclinical absorption testing, reinforcing their essential role in drug development pipelines.
HepG2 in Liver Function and Toxicology
Derived from hepatocellular carcinoma, HepG2 cells are a mainstay in hepatic studies. While they lack the complete metabolic profile of primary hepatocytes, their ease of culture and reproducibility make them attractive for high-throughput applications.
HepG2 cells are widely used to:
- Screen pharmaceuticals for hepatotoxicity.
- Investigate lipid metabolism and steatosis-related pathways.
- Model viral hepatitis and its impact on liver function.
Although not a perfect substitute for primary hepatocytes, HepG2 cells provide a practical system for preclinical toxicology and metabolic research.
Conclusion
These ten cell lines—HeLa, HEK293, CHO, SH-SY5Y, MCF7, THP1, A2780, HL-60, Caco-2, and HepG2—represent essential tools in the life sciences. Each contributes a unique window into biology, from cancer and immunology to pharmacology and toxicology. While they cannot capture the full complexity of human physiology, they form an indispensable bridge between basic science and clinical application. Their ongoing use highlights the delicate balance between convenience, reproducibility, and biological relevance that defines experimental research.
