Molecular Biology Research Highlights
Dr.
Y. Joseph Woo’s National Institutes
of Health and American Heart Association funded
laboratory is studying methods to harness endogenous
myocardial repair systems to treat the injured
heart. The following are among the novel myocardial
repair strategies under active investigation
in Dr. Woo’s laboratory:
Endothrlial Progenitor Stem Cell Mobilization
The laboratory is focusing on mobilizing endothelial
progenitor stem cells to produce microvascular
angiogenesis and restore blood flow to the
heart. Figure 1 depicts microvascular angiograms
from animal studies, including a control heart
and a heart from an animal that received a
bone marrow stimulant and an endothelial progenitor
stem cell chemokine.
Figure 1
Figure 1 – Immunohistochemical
labeling of newly formed blood
vessels, demonstrating the angiogenic
potential of enhanced endothelial
progenitor cell migration to compromised,
ischemic myocardium (J Thor Cardiovasc
Surg 2005, 130:321-329) |
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The treatment heart subsequently developed robust
microvasculature perfusion in the ischemic myocardium.
In many respects, this novel technique functions
as a “molecular coronary bypass graft.”
Cell-Cycle Regulator Protein Expression
Dr. Woo’s laboratory has developed another
approach to repairing the injured heart based
upon triggering heart cells to regenerate by
expressing the cell-cycle regulator protein cyclin
A2. Unique in its control at two major transitions
of the cell cycle, A2 is the only cyclin that
is completely silenced after birth in mice, rats
and humans. Using cyclin A2 expression via gene
transfer to induce cardiomyocyte cell cycle activation
yields improved myocardial function.
This strategy essentially tricks the heart into
regrowing itself. Figure 2 shows a cardiac cell
stimulated to undergo mitosis and regenerate
itself, a process normally occurring only during
fetal development.
Figure 2
 
Figure 3a Figure
3b
Figure 2 – Regenerating
cardiac muscle cells
Figure 3 – Shows echocardiograms
of rat hearts demonstrating improved
function of the cyclin expression
A) Control heart in systole
B) Cyclin treated heart
in systole demonstrating markedly
improved cardiac function
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