b2815 Tissue Engineering and Nanotheranostics “9.61x6.69”
76 Tissue Engineering and Nanotheranostics
During differentiation, hPSCs make a number of developmental
decisions to generate first the three germ layers (ectoderm,
mesoderm and endoderm), followed by subsequent decisions to
generate all of the body’s mature tissues. These differentiation
processes often involve a limited set of developmental cell signaling
pathways, which can be modulated by growth factors and small
molecules. Therefore, common methods of differentiating hPSCs
to therapeutic applicable cell lineages require application of specific
combination of growth factors and/or small molecules at distinct
differentiation stages. This chapter discusses recent progress
in the production of therapeutically applicable cells via directed
differentiation of hPSCs.
Keywords: Human pluripotent stem cells, induced pluripotent stem
cells, stem cell culture, directed differentiation, ectoderm, beta cells,
hepatocytes, lung progenitors, cardiomyocytes, hematopoietic cells,
endothelial cells.
1. Stem Cell Totipotency and Pluripotency
Fertilization occurs when the sperm fertilizes the egg. The fertilized
egg is imbued with the trait of totipotency. This totipotency allows
the cells to proliferate and differentiate into all the cell types that
make up the human body as well the extraembryonic cells that make
up the placenta. However, this level of differential potential only lasts
for the first few divisions of the zygote. Those cells, termed embry-
onic stem cells (ESCs), not associated with making the placental tis-
sue, are said to be in a state of pluripotency and can be obtained from
the inner cell mass during the blastocysts phase.
Pluripotent stem cells have the ability to become all cell types
within the human body. Upon differentiation, a cell’s fate is further
limited to ectoderm, mesoderm, or endoderm tissue types. Before
unraveling the production of each of these germ layers and their
derivative cell types, it is important to understand the characteristics
the characteristics of maintained pluripotency. Stem cell research
depends on strategies to maintain the pluripotent state. Otherwise,
these cells will lose pluripotency, due to spontaneous differentiation,
before researchers can definitively test their potential applications.