Abstract
SummaryThe possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC)-derived neural cells could be cultured in human cerebrospinal fluid (CSF) in order to better mimic the in vivo conditions. Our results showed that CSF altered the differentiation of hESC-derived neural cells towards glial cells at the expense of neuronal differentiation. The proliferation rate was reduced in CSF cultures. However, even though the use of CSF as the culture medium altered the glial vs. neuronal differentiation rate, the pre-existing spontaneous activity of the neuronal networks persisted throughout the study. These results suggest that it is possible to develop fully human cell and culture-based environments that can further be modified for various in vitro modeling purposes.
Highlights
Human neural stem cells are considered to serve as a promising supply for tissue/cell transplantation and for in vitro modelling of the nervous system, neurodevelopment studies, neurotoxicological screening of various substances, and drug screening and development (Gaspard and Vanderhaeghen, 2011; Yla-Outinen et al, 2010)
Human cerebrospinal fluid (CSF) supported neural cell growth whereas artificial CSF was detrimental to the cells After 8–15 weeks of differentiation the cell spheres were dissociated and replated in neural differentiation medium (NDM) on human laminin coated wells or micro electrode array (MEA) dishes
The cells grown in human CSF from neurologically healthy individuals (Fig. 1D,G) or NDM (Fig. 1C,F) remained viable, the cells grown in CSF reacted to the CSF change at 1 week time point after which recovery and increased gliogenesis was observed
Summary
Human neural stem cells are considered to serve as a promising supply for tissue/cell transplantation and for in vitro modelling of the nervous system, neurodevelopment studies, neurotoxicological screening of various substances, and drug screening and development (Gaspard and Vanderhaeghen, 2011; Yla-Outinen et al, 2010). Human derived neural cells can be isolated from various sources including aborted fetuses, adult human brain, and post-mortem brain tissue (Palmer et al, 2001; Piao et al, 2006; Roy et al, 2000) Even though these sources provide potentially adequate material for such investigations, one could claim that neural cells obtained either from human embryonic stem cells (hESC) or from induced pluripotent stem cells (iPCS) could more readily serve this purpose (Carpenter et al, 2001; Karumbayaram et al, 2009; Takahashi et al, 2007; Thomson et al, 1998; Yu et al, 2007). These, mainly hESC-derived, neural cells have already been tested in transplantation experiments in animal models (Daadi et al, 2008; Hicks et al, 2009; Keirstead et al, 2005; Sundberg et al, 2011), in neurotoxicity testing (Yla-Outinen et al, 2010; Zeng et al, 2006), and in development of efficient differentiation protocols (Lappalainen et al, 2010)
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