Biomedical Engineering Reference
In-Depth Information
organize in a core composed by proliferating c-Kit positive cells and a surrounding
layer of spontaneously differentiated cells that express markers characteristic of
cardiac, endothelial and mesenchymal cells. Their transplantation into immuno-
suppressed infarcted mice, improved cardiac function [
144
]. Finally, a new
population isolated from the embryo and adult atrium of the heart characterized by
the expression of the transcription factor Islet-1, but negative for the c-Kit or the
Sca1 markers, has been described [
145
]. As well as the other cell populations,
these cells possess self-renewing, clonogenic and multipotent abilities, including
cardiac differentiation potential.
In view of all this, it is of great relevance to better characterize these progen-
itors in order to be able to isolate them in a reproducible and consistent manner.
5.3.1.6 Fetal Cardiomyocytes
One of the first cell types to be investigated as potential candidates for cardiac
repair were fetal cardiomyocytes. Animal studies have shown that transplanted
fetal cardiomyocyte engraft into the heart tissue were electromechanically coupled
with the host cardiomyocytes improving the function of ischemic and globally
failing hearts [
146
,
147
]. However, the use of fetal cardiomyocytes presents
several concerns including availability, immunogenicity, and ethics, which
explains why other cell types have surpassed them as likely candidates for use in
cardiac repair [
98
].
5.3.1.7 Embryonic Stem Cells
The regenerative capacity of adult stem cells is quite limited, since they are able in
the best cases to contribute to vascular tissue but, in general, not to cardiac tissue.
Only a small population possesses robust cardiomyogenic potential, namely
embryonic stem cells (ESC), induced pluripotent stem cells, and the cardiac
progenitors present in the heart, as described above. Because both ESC and iPS
cells can be propagated indefinitely while still retaining their pluripotency, they are
a potentially inexhaustible supply of cardiomyocytes [
89
].
ESC are derived from the inner cell mass of mammalian blastocysts, and were
first isolated in 1981 from mice [
148
,
149
], and 17 years later from the human
species [
150
]. ESC have the broadest developmental potential (pluripotent) since
they can give rise to cells of all three embryonic germ layers. Furthermore,
functionally intact cardiomyocytes have been generated from human ESC in vitro
[
151
]. The ESC-derived cardiomyocytes injected into a mouse infarcted
myocardium formed stable grafts and subsequently contracted in synchrony with
adjacent cells [
152
]. In 2007 three different groups reported the formation of
human myocardium in infarcted rodent hearts using human ESC-derived cardio-
myocytes [
153
-
155
]. Studies with human ESC-derived cardiomyocytes have been
shown to engraft in infarcted mouse, rat, guinea pig and swine hearts, forming
