An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons
2010 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, Vol. 20, no 4, 1069-1082 p.Article in journal (Refereed) Published
Neuroscience, including research on Alzheimers disease, is hampered by the lack of suitable in vitro models to study the human nervous system. To counteract this, many attempts to differentiate cell lines into more neuron-like cells have been performed, resulting in partial expression of neuronal features. Furthermore, it has been reported that neuroblastoma cell lines lack mature isoforms of tau. Our aim was to develop an improved in vitro model, generating sustainable cells with morphology and biochemistry of human, mature neurons. To obtain cells with neuronal differentiation and function, we investigated the effect of combining three-dimensional culturing of SH-SY5Y cells in extracellular matrix (ECM) gel with several factors reported to have neuro-differentiating effects. This resulted in cells with apparent neuronal morphology with long, extensively branched neurites. Further investigation revealed expression of several neurospecific markers including synapse protein Sv2 and nuclear marker NeuN, as well as the presence of synapses and axonal vesicle transport. In addition, these cells expressed mature tau isoforms, and tau protein expression was significantly increased compared to undifferentiated cells, reaching levels found in adult human brain. In conclusion, we found that pre-treatment with retinoic acid followed by ECM gel culturing in combination with brain derived neurotrophic factor, neuregulin beta(1), nerve growth factor, and vitamin D-3 treatment generated sustainable cells with unambiguous resemblance to adult neurons. These cells also expresses adult splicing forms of tau with neuronal localization, making this cellular in vitro model useful in many areas of neuroscience research, particularly the Alzheimers disease field.
Place, publisher, year, edition, pages
Ios Press , 2010. Vol. 20, no 4, 1069-1082 p.
Alzheimers disease; differentiation; in vitro model; neuroblastoma; tau
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-58227DOI: 10.3233/JAD-2010-091363ISI: 000279539500012OAI: oai:DiVA.org:liu-58227DiVA: diva2:338051
Lotta Agholme, Tobias Lindström, Katarina Kågedal, Jan Marcusson and Martin Hallbeck, An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons, 2010, Journal of Alzheimer's Disease, (20), 4, 1069-1082.
Copyright: Ios Press