Nanotissue Engineering of Neural Cells - Stem-Cell Nanoengineering - page 250

Chapter 15
Nanotissue Engineering of Neural Cells
Sasan Jalili-Firoozinezhad 1,2 , Fahimeh Mirakhori 1,3 , and Hossein Baharvand 1
1 Department of Stem Cells and Developmental Biology at Cell Science Research Center,
Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
2 Departments of Surgery and of Biomedicine, University Hospital Basel, University of Basel, Basel,
Switzerland
3 School of Biology, College of Science, University of Tehran, Tehran, Iran
Introduction
Stem-cell niches form highly complex, dynamic microenvironments with numerous factors
involved, in which cells must constantly interact and reply back in response to the state of
the tissue. These specialized regions provide physical, structural, and architectural cues in
the form of a specialized basal lamina and various extracellular matrix (ECM) components,
which sequester growth factors and other bioactive molecules to modulate signaling-molecule
availability [1]. Moreover, the presence of a different range of supportive cells (e.g., astrocytes,
ependymal cells, and endothelial cells) and differentiated cells (e.g., different types of mature
neurons) within stem-cell niches add further complexity. They act to integrate signals from
within the niche environment and provide proper responses to modulate resident stem-cell
behavior through a dynamic feedback loop [2]. Supporting and differentiated cells can also
further modify the niches by their paracrine secretion, including growth/trophic factors,
mitogens, morphogens, and differentiation cues [3-7]. Additionally, different conformations
and densities of the matrix, matrix stiffness, and the location of cells within these niches can
affect stem-cell behavior [8-11].
There has been much progress in the attempt to confirm the existence of neural stem-
cell (NSC) niches in regions of the adult central nervous system (CNS), such as the
subventricular zone [2] and dentate gyrus [12]. However, individual components that form
these constantly changing niches, specific cell-microenvironment interactions and the
mechanisms by which these all interact together to modulate precise control of the NSC
fate are still largely unknown. Therefore, for recapitulating a complex synthetic NSC niche
environment, a much more comprehensive understanding of the exact nature of neuronal
niches, including spatial organization and dynamic modulation of cells, soluble factors,
and the matrix, is required [13]. However, recreating even an elegantly simple NSC niche
is invaluable for in vitro NSC self-renewal, assessment for differentiation, and its potential
for regenerative medicine.
In this chapter we provide an extensive overview on ongoing efforts in nanotechnology
related neural-tissue engineering. In the first section, different aspects of biological