Biomedical Engineering Reference
In-Depth Information
Role of ESCs in Repair of the Heart
Investigators have been looking for a relatively simple way to help restore the
functioning of hearts damaged by chemotherapy, which can occur in up to 10% of
cancer patients treated with chemotherapy drugs. ESCs are known to repair dam-
aged hearts. In mice, hESCs use different methods to morph into two kinds of cells
needed to restore heart function: cardiac muscle cells that contract the heart as well
as the endothelial cells that line blood vessels found throughout the organ. In one
study, 2 months after mice with ailing hearts were treated with hESCs, about 2% of
cells in their heart showed evidence of a human genetic marker (Zhang et al.
2004
).
hESCs primarily fuse onto mouse cardiac cells to produce new muscle cells that
have both human and mouse DNA. But to form new blood vessel cells, they dif-
ferentiate by themselves, presumably to patch damaged mouse blood vessels with
human cells. These findings should help resolve debate within the field as to
whether ESC transfer actually creates new types of cells that last within a heart.
ESCs represent a source for cell-based regenerative therapies of heart failure.
The pluripotency and the plasticity of ESCs allow them to be committed to a car-
diac lineage following treatment with growth factors of the transforming growth
factor (TGF)-b superfamily. French researchers have designed a protocol to turn on
expression of cardiac-specific genes in undifferentiated murine ESCs stimulated
with BMP2 and/or TGF-b (Zeineddine et al.
2005
). Cell commitment results in a
significant improvement in spontaneous cardiac differentiation of ESCs both
in vitro and in vivo. In further studies, these researchers have successfully trans-
planted ESCs from mice to repair myocardial infarction in sheep (Menard et al.
2005
). Sheep in ESC-treated group had healthier heart tissue after 1 month com-
pared with sheep who did not receive ESC transplantation (the control group).
There was no rejection or tumor formation following the procedure. This shows
that mouse ESCs could be transplanted into larger mammals to regenerate damaged
heart cells, strengthening the possibility that ESCs could one day be used to repair
heart cells in humans.
Studies in animal models have shown that transplanted mouse ESCs can regen-
erate infarcted myocardium in part by becoming cardiomyocytes, vascular smooth
muscle, and endothelial cells that result in an improvement in cardiac structure
and function (Singla et al.
2006
). Therefore, ESCs hold promise for myocardial
cellular therapy. One important finding of this study is that the implanted cells did
not result in tumor formation, which is one of the primary safety concerns for
stem cell therapy. That undifferentiated hESCs can survive in rat hearts during
myocardial infarction without the formation of teratoma, has been demonstrated
by using undifferentiated GFP-transgenic hESCs (Xie et al.
2007
). A laser-capture
microscope was used to dissect the GFP-positive cell area from the hESC-injected
hearts to document the expression of human cardiac-specific genes including
GATA-4, Nkx-2.5, and cardiac troponin I. However, like cancer cells, ESCs have
a capacity to reproduce indefinitely, and scientists must perfect cell transplant
methods that are safe before the therapy can be attempted in human patients.
Future studies will explore ways to refine the cell types used in treating heart
disease to enhance safety.
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