247cardiac progenitor (neurospheres and cardiospheres, respectively) also showed
improved features compared to monolayer cultures (Messina et al. 2004 ; Reynolds
and Rietze 2005 ; Marban and Cingolani 2012 ; Baraniak et al. 2012 ). Due to all
these reasons, engineering of the niche specific for each stem cell type becomes
critical in avoiding the failure of stem cell-based therapies in humans.
13.2.1 Technologies Based on the Stem Cell Niche
Several groups have engineered the typical niche of the human body using stem
cells, including the blood brain barrier and brain (Lippmann et al. 2012 ; Adriani
et al. 2016 ), lung airway (Benam et al. 2016 ) and the hematopoietic niche (Torisawa
et al. 2014 ). However, there are still several challenges in engineering a fully-
controlled stem cell niche of these and other vital organs, such as the brain, the heart
and the immune system. The most challenging features to overcome are: (i) replicat-
ing physiologically-relevant culture conditions without affecting the robustness of
the cellular response to the experimental stimuli, such as blood flow and tethering
effects of the extracellular matrix during development; (ii) stem cells limited sur-
vival in new culturing conditions and/or following engraftment; (iii) maintaining a
specific phenotype in culture. Factors determining optimal engineering of 3D cul-
tures of stem cells have been previously described, and include cell composition,
gradient of oxygen and nutrients, growth factors, extracellular matrix and stiffness,
Fig. 13.1 Engineering of the stem cell niche: approaches and applications (adapted from Gentile
2016 )
13 Current Technologies Based on the Knowledge of the Stem...