What Are SH-SY5Y Cells and How Are They Used?

SH-SY5Y cells are a widely used human cell line in neurobiology research. They serve as a valuable laboratory model for studying nerve cell function and responses.

Origin and Cellular Profile

The SH-SY5Y cell line originated from a bone marrow biopsy obtained from a four-year-old female patient diagnosed with neuroblastoma, a cancer that forms in nerve tissue. This biopsy led to the establishment of the parent cell line, SK-N-SH, in 1970. SH-SY5Y is the third subclone derived from this original SK-N-SH line, selected for its neuroblast-like characteristics.

These cells are classified as neuroblast-like, possessing characteristics similar to immature nerve cells. In culture, SH-SY5Y cells grow adherently, attaching and spreading on the bottom surface of a culture dish, though some cells may also grow in suspension. They form clumps of cells with short, fine processes resembling neurites.

The Process of Differentiation

A distinguishing feature of SH-SY5Y cells is their ability to undergo differentiation, a process where immature cells develop characteristics more akin to mature, functional neurons. This capability makes them useful for neurological studies. During differentiation, the cells exhibit significant morphological and biochemical changes.

The most common method for inducing differentiation involves treating the cells with Retinoic Acid (RA), a derivative of vitamin A, which promotes cellular maturation and inhibits rapid cell division. Other agents, such as brain-derived neurotrophic factor (BDNF), phorbol esters like 12-O-tetradecanoyl-phorbol-13 acetate (TPA), or dibutyryl cyclic AMP (dbcAMP), can also be used to enhance or direct differentiation towards specific neuronal subtypes. As they differentiate, SH-SY5Y cells reduce their proliferation rate and begin to extend longer processes called neurites, which resemble the axons and dendrites of mature neurons. They also start expressing proteins found in mature neurons, such as neuron-specific enolase, β-III tubulin, microtubule-associated protein 2 (MAP2), tyrosine hydroxylase, and synaptophysin.

Applications in Neurological Research

SH-SY5Y cells are applied in neurological research to investigate the mechanisms of various brain disorders and test potential therapies. An application involves modeling Parkinson’s disease, where scientists expose these cells to neurotoxins like MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) or rotenone to induce neuronal damage. This allows researchers to study cellular pathways involved in neurodegeneration, such as mitochondrial dysfunction and oxidative stress, and to evaluate protective compounds.

The cells are also used in Alzheimer’s disease research by treating them with amyloid-beta peptides to mimic the plaque formation seen in the disease. This enables the study of how these plaques affect neuronal viability, gene expression, and cellular processes like apoptosis and autophagy. Beyond specific diseases, SH-SY5Y cells serve as a model for neurotoxicity screening, to assess the harmful effects of new drugs, environmental chemicals like pesticides (e.g., glyphosate), or pollutants on human neuronal cells.

Limitations as a Scientific Model

Despite their widespread use, SH-SY5Y cells have limitations as a scientific model. Their origin from a cancerous tumor means they retain some cancer-like properties, which can influence their growth, metabolism, and responses compared to healthy, primary human neurons. This cancerous background results in genetic instability, with the cells possessing an abnormal chromosome 1, which can lead to variability in experimental outcomes across different laboratory passages.

While these cells can be differentiated to become neuron-like, they do not fully replicate the complex synaptic networks and intricate three-dimensional microenvironment found in the human brain. This means they may not fully mimic the in vivo responses of neurons. Researchers must account for these inherent differences when interpreting results and extrapolating findings to human physiology.

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