Development of a 3D in-vitro model for Alzheimer’s disease: Behavioral investigation of SH-SY5Y cells in brain-mimicking matrices

Typ
Examensarbete för masterexamen
Master Thesis
Program
Biomedical engineering (MPBME), MSc
Publicerad
2017
Författare
Hardselius, Erik
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Worldwide over 50 million people are suffering from Dementia and 60-70% of these cases are believed to be liked to Alzheies disease AD (1). Studies show that people suffering from repeated or severe head trauma (2), such as professional oes, ad people ith Dos sdoe(3, 4) ae oe poe to deelop Alzheies disease later in life. One common feature in these medical cases is an altered extracellular matrix in the brain due to either trauma or genetic factors. Understanding the mechanisms behind AD have has proven a challenge to the scientific community due to the lack of a functional disease model for AD. So far, the full AD progression has yet to be adequately modelled in a controlled setting, such as an in vitro or in vivo model, even though at least one promising candidate has been reported by Choi et al. utilizing 3D-cell culturing system that displays increased levels of both intracellular phosphorylated-tau proteins and extracellular amyloid β plaques compared to a 2D control (5). In this work a bare bones tuneable brain 3D-cell model protocol is presented and evaluated using three different cell lines of differentiated SH-SY5Y neuroblastoma cells. The most promising conditions in the matrix show neuron-like cells that exhibit comparable morphology to those presented by previous models but in a more controlled and well defined environment. The model makes promising use of hyaluronic acid in a 3D-matrix seeded with differentiated cells. Studies performed in the new model hints towards an ultimately cytotoxic interaction between Aβ and ECM components, which encourages further investigations of neuron/ECM/Aβ interactions in AD
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Medicinsk bioteknologi , Medical Biotechnology
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