Biomedical Engineering Reference
In-Depth Information
By the activation of specific receptors and signaling pathways, hESCs could differentiate to
cartilage, liver, neural tissues, hepatocyte-like cells and blood vessels under three-dimensional
supportive polymer scaffolds [15, 51]. Caspi
et al
. showed that three-dimensional polymeric
scaffolds that generate a tissue-engineered muscle construct can be used for myogenic tissue
replacement therapy in the hESCs-differentiated vascularized cardiac muscles [52]. In addition,
by applying a three-dimensional nanofiber peptide scaffold to induce differentiation, Garreta
et al.
observed increased osteoblast-like cell differentiation in mESCs by using embryoid body
(EB) formation in the presence of osteogenic differentiation media [53].
In comparison to two-dimensional cultivation conditions, the expression of neuronal
markers is higher in mESCs-derived neuronal cells that were differentiated on highly porous
three-dimensional scaffolds [54].
Embryo-body formation is a typical protocol used in nanotechnology studies for induction
of ESC differentiation. Kabiri
et al
. showed that EBs derived from mESCs and seeded on
conductive nanofiber scaffolds, differentiated to mature neuronal cells in the presence of
retinoic acid (RA) [55]. In generated mouse EBs, silica nanoparticles were reported to
hamper differentiation to contracting cardiomyocytes cells [56]. In the absence of EB
formation, spontaneous differentiation of hESCs into ectodermal germ-layer and neuronal
morphology was observed onto composite material collagen-carbon nanotube fibrils [57].
It has been observed that biodegradable scaffolds support neuronal and vascular
differentiation of hESCs in the presence of RA, nerve growth factor, and neurotrophin 3
[58]. In addition, stiffness of polydimethylsiloxane substrates was reported to enhance the
expression of primitive streak markers (the process of gastrulation) and early mesendoder-
mal markers, Brachyury, Mixl1, and Eomes in mESCs [59]. Also, the culture of mESCs on
multilayer nanofilm increased the expression of mesodermal markers such as Brachyury
and Goosecoid [48]. Therefore, nanostructures can be applied as extracellular matrix
scaffolds that could discriminate the fate of PSCs for differentiation to several lineages.
Conclusions
The self-renewal and differentiation potential of pluripotent stem cells and, on the other
hand, functional application of nanotechnology in stem-cells research will provide new
horizons towards regenerative medicine and stem-cell therapy in the future.
Although iPSCs are similar to ESCs, there are some challenges regarding the methods to
establish iPSCs. Up to now, most stem-cell scientists have used integrating viruses to generate
these cells, and additionally there are some oncogenes used in induction cocktails of iPSCs.
However, there are some rare reports indicating establishment of iPSC lines without using
oncogenes and also viruses [7, 8]. In addition, safer iPSC lines have been produced with non-
integrating vector transfection, and also by using the mRNA version of the Yamanaka
factors, as well as the application of small molecules [7]. Despite these bottlenecks, the iPSC
technique is very strong in modeling diseases
in vitro
and also for patient-specific drug dis-
covery. There are several reports indicating modeling of diseases from neurological, immune
system, genetic, hematological, and also psychiatric disorders based on disease-specific IPSCs
[60]. In some of these studies, differentiated iPSCs could successfully mimic the phenotype of
the diseases
in vitro
[60]. This iPSCs-related
in vitro
modeling system can be used to better
investigate the pathology of diseases and as a more realistic drug-screening approach.
Human SSCs are another potential source of pluripotent/multipotent stem cells, which
could be used in human regenerative medicine in the future. According to Ko
et al
. [61],
a dilemma arises concerning the real character of human adult GSCs (haGSCs), and they
suggested that these cells are simple fibroblasts. In the study by Chikovskaya
et al
. [62], the
