Three-dimensional neuronal cell culture: in pursuit of novel treatments for neurodegenerative disease
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iomaterials for 3D Cell Biology Prospective Article
Three-dimensional neuronal cell culture: in pursuit of novel treatments for neurodegenerative disease Sarah-Sophia D. Carter, ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, University of Wollongong, NSW 2522, Australia; Utrecht University, Utrecht, The Netherlands Xiao Liu, Zhilian Yue, and Gordon G. Wallace, ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, University of Wollongong, NSW 2522, Australia Address all correspondence to Gordon G. Wallace at [email protected] (Received 23 June 2017; accepted 5 September 2017)
Abstract To gain a better understanding of the underlying mechanisms of neurological disease, relevant tissue models are imperative. Over the years, this realization has fuelled the development of novel tools and platforms, which aim at capturing in vivo complexity. One example is the field of biofabrication, which focuses on fabrication of three-dimensional (3D) biologically functional products in a controlled and automated manner. Herein, we provide a general overview of classical 3D cell culture platforms, particularly in the context of neurodegenerative disease. Subsequently, the focus is put on bioprinting-based biofabrication, its potential to advance 3D neuronal cell culture and, to conclude, the relevant translational bottlenecks, which will need to be considered as the field evolves.
Introduction The vast majority of our current understanding of biologic phenomena comes from routine classical cell culture experiments; growing of cells onto flat and rigid two-dimensional (2D) substrates. Even though these efforts have provided the research community with valuable insights into the mechanisms underlying a variety of biologic processes, it is nowadays widely accepted that knowledge obtained from these studies might be too reductionist to accurately translate to the human situation.[1,2] Growing cells onto 2D substrates deviates significantly from the dynamic three-dimensional (3D) in vivo situation; cells lack tissue-specific polarity, have limited contact with neighboring cells, and are exposed to non-physiologically uniform diffusion kinetics, which together alter how cells perceive and respond to their surrounding microenvironment (Fig. 1).[3–5] This discrepancy between traditional in vitro culture conditions and the in vivo environment has been recognized among a variety of research areas, including the area of neuroscience and more specifically neurological disease, the latter presenting a great challenge in modern medicine.[6]
A glance at our nervous system Our nervous system encompasses two main cell types, neurons and glial cells, which both have a crucial role in nervous system functioning.[8,9] Neurons are highly polarized cells, responsible for the transfer and processing of electrical and chemical signals that regulate body function. According to their function, neurons can be classified into sensory neurons, mo
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