Functionality of Human Stem Cell-Derived Neuronal Networks
Biomimetic Environment & Characterization



By Laura Ylä-Outinen
April 2012
Tampere University Press
Distributed by Coronet Books Inc.

ISBN: 9789514487552
148 pages

$85.00 Paper original



Cell transplantation therapies provide new hope for central nervous system deficits. In particular, stem cells are a potential source for new regenerative therapies. Human embryonic stem cells (hESC) are considered to be useful for transplantation therapies as they can be successfully differentiated into central nervous system cell types, i.e., neurons, astrocytes, and oligodendrocytes, in sufficient quantities. Another interesting pluripotent cell type, human induced pluripotent stem cells (hiPSCs), was recently identified as a potential source for clinical applications. Both of these pluripotent stem cell types also have rather high potential for in vitro platforms. Thus, these cells can be used for toxicology studies, drug screening, developmental research, and patient-specific drug research and diagnostics.

Before the full benefits of these cells can be realized, however, they must be intensively studied in a more in vivo like, i.e., biomimetic, environment, in three-dimensional (3D) structures. In 3D, cells interact and behave more like their in vivo counterparts. Thus, for in vitro models as well as research aimed at regenerative medicine, cells should be tested in a 3D environment.

In the present study, a large variety of natural and synthetic biomaterials as growth surfaces or 3D matrices were tested for application to hESC-derived neuronal cells. One synthetic self-assembled peptide hydrogel, PuraMatrix, was also tested in 3D. Human ESC-derived neuronal cells grew and matured in this 3D scaffold. One of the most important functions of neuronal cells, in addition to their chemical activity, is their electrical activity. Thus, the characteristics of hESC- or hiPSC-derived neuronal cells must be evaluated at the functional, i.e., electrophysiologic level. The electrical activity of hESC-derived neuronal cells at the network level was evaluated using a microelectrode array (MEA) method and the cell culture measurement environment was further improved for that specific cell type. The electrical measurement methods can be used for in vitro toxicology studies, as they allow for continuous, noninvasive, and sensitive characterization. Here, we evaluated and confirmed the validity of hESC-derived neuronal cells and the MEA measurement platform for in vitro neurotoxicity analysis.

The electrical activity of hESC-derived neuronal cells was also evaluated in a 3D scaffold in which cells were encapsulated inside a hydrogel. The cells formed a functional neuronal network in this biomimetic 3D environment, thus providing a platform for in vitro toxicology studies the results can be applied to further improve the field of neuronal tissue engineering.

More detailed information about the activity of hESC-derived neuronal cells and their networks are needed before these cells can be reliably used in transplantation therapies. Moreover, further optimization is needed for cell differentiation and maturation processes as well as for data analysis before these cells on MEA can be used as a valid in vitro neurotoxicity platform.

 

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