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Title: Modelling healthy and injured human central nervous system using human neural stem cells in 2D and 3D cultures
Author: Vagaska, B.
ISNI:       0000 0004 8502 6495
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2015
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The complexity of the human central nervous system (CNS), together with the limited possibility of experimentally manipulating it in vivo pose major challenges to studying human neural development, neurodegenerative diseases and responses to injury at the cellular and molecular level. The need for a reliable and readily available human CNS models can be solved by three-dimensional (3D) cell cultures that provide a more physiologically relevant environment than conventional 2D cultures. The aim of this work was to develop 3D culture models of normal and injured human CNS using human neuroblastoma cell lines and human foetal brain-derived neural stem cells (hNSCs). Characterization of hNSCs in comparison with mesenchymal stem cells highlighted differences in their immunogenicity, and led to the discovery of a novel subset of hNSCs co-expressing the neural marker SOX2 and MHC class-II antigen in vitro as well as in vivo during human CNS development. Optimal conditions for culturing undifferentiated and differentiated hNSCs in 3D differed from those reported for animal cells. hNSCs were not viable in collagen gels, but grew and differentiated in combined collagen I and/or Matrigel hydrogels. hNSCs and neuroblastoma cells showed distinct behaviour and gene expression in different matrices and in 3D as compared to 2D cultures, highlighting the importance of cell-matrix interactions and culture architecture. An in vitro hypoxia-ischemia injury model using oxygen-glucose deprivation was established in 3D cultures. Injury in these in vitro systems led to up-regulation of a cell death-associated citrullinating enzyme, peptidylarginine deiminase-3, paralleled to that observed in in vivo animal injury models. The 3D culture models developed provide novel platforms for studying human neural cell biology, including injury responses, and for neuroprotective drug testing.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available