Biomedical Engineering Reference
In-Depth Information
mammalian heart, including mice and humans, has been reported.
Various populations of cardiac stem/progenitor cells, including Sca-
1(+), side population, cardiac sphere, and isl-1(+) cells, were isolated
from the heart and differentiated into beating cardiomyocytes.
However, a clonal expansion system fully maintaining their
cardiac differentiation potential has not been established, which
might hamper the application of cardiac stem/progenitor cells in
myocardial tissue engineering.
Despiteethicalandmoralissues,thebenefitsofembryonic
stem (ES) cells, including pluripotency and unlimited self-renewal,
mightprovideasolutionforcollectingsufficientcardiomyocytes
for heart tissue repair [1, 2]. Furthermore, the recent discovery
of induced pluripotent stem (iPS) cells, which are reprogrammed
from somatic cells to ES-like cells, might enable the creation of
autologous ES-like cells and resolve the ethical issues of ES cell
usage[3,4].Althoughtheirefficacyremainselusive,robuststudies
have proved cardiomyocyte differentiation from ES/iPS cells.
However, the remaining undifferentiated cells may be associated
with tumor formation after transplantation. Because the adult
human left ventricle contains ~4 billion cardiomyocytes, developing
technologies for effective cardiomyocyte differentiation, expansion,
andpurificationfromstemcellsisrequiredtoreconstructaninjured
myocardium. Therefore, ES/iPS cells may be the most potent and
practical cell sources for this purpose. ES/iPS cell differentiation
into multiple cell lineages partially follows embryonic development,
and instructive extracellular signals that contribute to cardiac
development are known to be spatiotemporally regulated. Here, we
begin with a brief description of heart development in mice and then
review the recent progress of cardiac differentiation processes, with
an emphasis on signaling molecules.
In embryonic development, the cardiovascular lineage is derived
from the mesoderm. During gastrulation, the mesoderm and the
endoderm are initiated by epiblast cell migration through the
primitive streak. Mesodermal cardiac cells are derived from epiblast
cells in the distal region of the primitive streak [5]. These progenitor
cells migrate to the embryonic anterior region and form the cardiac
crescent until embryonic day (E) 7.75 (Fig. 2b.1) [6]. Cells at the
lateral edge of the cardiac crescent migrate toward the ventral
midline, and cells on the opposite side fuse to form the heart tube.
The heart tube consists of an outer layer of cardiomyocytes and an
