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in PDMS molds (Boudou et al. 2012 ) or non-adherent plates (Ravenscroft et al.
2016 ); or (iii) fully bioprinted system (Lind et al. 2016 ). Recently, bioprinted vascu-
larized cardiac tissue have been generated by plating iPSC-cardiomyocytes on top
of bioprinted vascular network of endothelial cells (Zhang et al. 2016 ). Further
maturation of iPSC-cardiomyocytes into a more adult phenotype has been investi-
gated via electrical, for instance either with electrical impedence spectroscopy
(Burgel et al. 2016 ) or using electrically conductive silicon nanowires (e-SiNWs)
(Tan et al. 2017 ).
13.2.4 Genetic Approaches to Engineer the Stem Cell Niche
Reprogramming of stem cells in 3D cultures via CRISPR or TALEN technology has
the potential to unveil mechanisms regulating the stem cell niche (Sun and Ding
2017 ; Yin et al. 2016 ; Gonzalez 2016 ). Reprogramming of somatic cells into stem
cells is dependent on donor age, a factor that limits the use of stem cell-based thera-
pies in humans (Lo Sardo et al. 2017 ). However, Schwank et al. ( 2013 ) have recently
demonstrated how the use of CRISPR genome editing in 3D cultures generated
from patients with cystic fibrosis (CF) could advance tissue repair and functionality.
In this study, targeted genome editing of intestinal spheroid cultures from two CF
patients with CRISPR-Cas9-mediated homology-directed repair corrected the
mutation (deletion of phenylalanine at position 508) of the CF trans-membrane con-
ductor receptor (CFTR), the primary cause of the disease, supporting the feasibility
an autologous gene therapy strategy using 3D cultures in patients with hereditary
diseases (Yui et al. 2012 ). Similarly, gene editing in 3D cultures could be utilized as
in vitro disease models to identify novel molecular targets for future therapies, as
recently demonstrated in genome-edited human intestinal epithelial organoids
(Matano et al. 2015 ).
13.2.5 Synthetic Biology and the Stem Cell Niche
Synthetic biology allows the integration of highly dynamic and transient multiple
stem cell niches at the same time during embryogenesis, which generated promising
results in regulating the stem cell niche in vitro with direct application for future
stem cell-based therapies (Purcell and Lu 2014 ). Thanks to the integration between
the synthetic and biological components, tissue homeostasis or diverse functions of
the stem cell niche can now be controlled by transcriptional activators and/or repres-
sors, and other novel mechanisms, such as: (i) switches; (ii) memory elements, (iii)
cascades; (iv) time-delayed circuits; (v) oscillators; (vi) logic gates; (vii) artificial
gene circuits (Cheng and Lu 2012 ; Lohmueller et al. 2012 ; Purcell and Lu 2014 ;
Siuti et al. 2013 ). For instance, biosensors generated using synthetic biology can
record the history of cellular exposure to either individual or a sequence of
D. Mawad et al.