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SH-SY5Y Cell Line

Repository ID: CL-HUM-003


Quick Facts​

ParameterInformation
Cell LineSH-SY5Y
SpeciesHuman (Homo sapiens)
Tissue of OriginBone marrow metastasis of neuroblastoma
Disease AssociationNeuroblastoma
Cell TypeNeuroblast-like
Growth ModeAdherent
MorphologyMixed neuroblast-like and epithelial-like populations
Typical MediumDMEM/F12 + 10% FBS
Doubling Time30-40 hours
Passage70-80% confluency
Main UseHuman neuronal model for neuroscience research

Overview​

SH-SY5Y is one of the most widely used human neuronal cell models in biomedical research. Derived from a human neuroblastoma, it combines the ease of culturing an immortal cell line with the ability to acquire neuron-like characteristics through differentiation.

Because of its human origin and experimental versatility, SH-SY5Y is extensively used to investigate neuronal development, neurodegenerative diseases, neurotoxicity, oxidative stress, and neuropharmacology.

Although differentiated SH-SY5Y cells resemble neurons, they remain a transformed neuroblastoma-derived cell line and do not fully replicate mature human neurons.


Origin​

  • Derived as a subclone of the human neuroblastoma cell line SK-N-SH.
  • Successive subcloning enriched cells with neuronal characteristics.
  • Established as a reproducible human neuronal model for neuroscience research.

Unique Biology​

A defining characteristic of SH-SY5Y cells is their ability to undergo neuronal differentiation.

Following treatment with agents such as retinoic acid (RA) or brain-derived neurotrophic factor (BDNF), SH-SY5Y cells develop:

  • Extended neurites
  • Reduced proliferation
  • Increased neuronal marker expression
  • More mature neuronal morphology

Undifferentiated cultures typically contain a mixture of neuroblast-like (N-type) and substrate-adherent (S-type) cells. The proportion of these populations and the differentiation protocol used can influence experimental outcomes.

Because they express many neuronal proteins while remaining easy to culture, SH-SY5Y cells serve as a practical bridge between conventional immortalized cell lines and primary neurons.


Culture Considerations​

Typical culture conditions include:

  • DMEM/F12
  • 10% Fetal Bovine Serum
  • 37°C
  • 5% CO₂

Cells grow as adherent cultures and are generally passaged at 70-80% confluency. Overconfluent cultures may undergo phenotypic changes and show reduced differentiation efficiency.

Experimental reproducibility depends heavily on maintaining consistent passage numbers and standardized differentiation protocols.


Major Applications​

SH-SY5Y cells are extensively used for:

  • Neurodegenerative disease research
  • Alzheimer's disease
  • Parkinson's disease
  • Huntington's disease
  • Amyotrophic lateral sclerosis (ALS)
  • Neurotoxicity studies
  • Oxidative stress research
  • Dopaminergic neuron research
  • Neuropharmacology
  • Drug discovery
  • Mitochondrial biology

Strengths​

  • Human-derived neuronal model
  • Easy to culture and maintain
  • Amenable to neuronal differentiation
  • Cost-effective alternative to primary neurons
  • Extensive neuroscience literature
  • Suitable for high-throughput studies

Limitations​

  • Derived from neuroblastoma rather than normal neurons
  • Differentiated cells do not fully reproduce mature neuronal physiology
  • Experimental outcomes depend on differentiation protocol
  • Lack interactions with glial cells and neural circuits present in vivo

References​

  1. Ross RA, Spengler BA, Biedler JL. Coordinate Morphological and Biochemical Interconversion of Human Neuroblastoma Cells. Journal of the National Cancer Institute.
  2. Xicoy H, Wieringa B, Martens GJM. The SH-SY5Y Cell Line in Parkinson's Disease Research: A Systematic Review. Molecular Neurodegeneration.
  3. Kovalevich J, Langford D. Considerations for the Use of SH-SY5Y Neuroblastoma Cells in Neurobiology. Methods in Molecular Biology.
  4. Freshney RI. Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications.
  5. ATCC Cell Line Database.
  6. Cellosaurus Cell Line Knowledge Resource.
  7. ECACC Cell Line Collection.