“9.61x6.69” b2815 Tissue Engineering and Nanotheranostics
Directed Differentiation of Human Pluripotent Stem Cells 89
highlighted the potential clinical application of a differentiation pro-
tocol for lung progenitors and lung epithelial cells for patient specific
drug testing and human disease modeling.^50
In 2012, Wong et al. provided another successful differentiation
protocol producing airway epithelial cells from a CF patient derived
iPSCs and hESCs.^51 This protocol further differentiated lung pro-
genitors and implemented an air liquid interface in vitro culture
technique to further mature the lung epithelial cells.^51 They used the
CF trans-membrane conductance regulator (CFTR) gene to func-
tionally assay their resulting airway epithelial cells, and achieved
approximately 30% efficiency in deriving CFTR functional epithelial
cells.^51 However, the lack of functionality tests represents a key bar-
rier in the development of lung epithelial differentiation methods.^47
While CFTR function provides an interesting application of a disease-
specific manifestation to determine lung epithelial function, addi-
tional functional assays will be necessary to further characterize this
cell type.
3.3. Mesoderm
After the invagination of the blastula forms the basis of the endoderm
and ectoderm, mesenchymal cells begin to populate the space in
between, slowly forming a third germ layer in the center, the meso-
derm. The mesoderm gives rise to all muscle types, connective tissues,
kidneys, vascular endothelium, and hematopoietic cells. Much like
endoderm, the mesoderm also has a unique pattern of signaling
required to initiate its specification. The progress of directed differen-
tiation techniques for cardiomyocytes, hematopoietic cells, and
vascular endothelial cells derived from this embryonic germ layer is
outlined below.
3.3.1. Cardiomyocytes
Cardiomyocytes are the terminally differentiated heart muscle cells.
These cells are characterized by spontaneous contraction in vitro and
syncytium behavior. Cardiomyocytes provide a desirable cell type for
