257environmental signals, creating a memory within the bioengineered tissue (Siuti
et al. 2013 ). This memory may then be used for the delivery of exogenous signals
and apply them in sequence rather than simultaneously, which may help to over-
come several limitations occurring with stem cells, such as limited survival and
engraftment upon transplantation.
13.3 Conclusions and Future Perspectives
Engineering of three-dimensional niche with defined features demonstrated to
improve survival and architectural structure of stem cells, leading to a more physi-
ological microenvironment and behavior. Due to the remaining hurdles in recapitu-
lating in one in vitro model all the biological, morphological and physiological
features typical of the in vivo stem cell niche features (Hunsberger et al. 2015 ),
future studies aiming at integrating all the different physicochemical and genetic
cues typical of the 3D niche described in this chapter should be considered before
engineering stem cell-based therapeutics for humans. Furthermore, engineering of
in vitro systems including bioprinted organs-on-a-chip for drug discovery and toxic-
ity testing using stem cells may benefit from the integration of the abovementioned
features. This information will become undoubtedly even more relevant with the
upcoming interest in “precision medicine” and bio-banking of patient-specific 3D
mini-organs (Bredenoord et al. 2017 ).
References
Adriani G, Ma D, Pavesi A, Kamm RD, Goh EL (2016) A 3D neurovascular microfluidic model
consisting of neurons, astrocytes and cerebral endothelial cells as a blood-brain barrier. Lab
Chip 17(3):448–459
Alperin C, Zandstra PW, Woodhouse KA (2005) Polyurethane films seeded with embryonic stem
cell-derived cardiomyocytes for use in cardiac tissue engineering applications. Biomaterials
26:7377–7386
Arshi A, Nakashima Y, Nakano H, Eaimkhong S, Evseenko D, Reed J, Stieg AZ, Gimzewski JK,
Nakano A (2013) Rigid microenvironments promote cardiac differentiation of mouse and
human embryonic stem cells. Sci Technol Adv Mater 14(2):025003
Baraniak PR, Cooke MT, Saeed R, Kinney MA, Fridley KM, Mcdevitt TC (2012) Stiffening of
human mesenchymal stem cell spheroid microenvironments induced by incorporation of gela-
tin microparticles. J Mech Behav Biomed Mater 11:63–71
Battista S, Guarnieri D, Borselli C, Zeppetelli S, Borzacchiello A, Mayol L, Gerbasio D, Keene
DR, Ambrosio L, Netti PA (2005) The effect of matrix composition of 3D constructs on embry-
onic stem cell differentiation. Biomaterials 26:6194–6207
Benam KH, Novak R, Nawroth J, Hirano-Kobayashi M, Ferrante TC, Choe Y, Prantil-Baun R,
Weaver JC, Bahinski A, Parker KK, Ingber DE (2016) Matched-comparative modeling of nor-
mal and diseased human airway responses using a microengineered breathing lung chip. Cell
Syst 3:456–466 e4
Bhatia SN, Ingber DE (2014) Microfluidic organs-on-chips. Nat Biotechnol 32:760–772
13 Current Technologies Based on the Knowledge of the Stem...