Biomedical Engineering Reference
In-Depth Information
Mechanism of the Benefit of Cell Therapy for Heart Disease
In spite of tremendous activity in cell therapy of cardiac disease, the mechanism for
potential therapeutic effect is unclear. A growing body of evidence suggests that the
improvement in cardiac function is largely independent of cardiac muscle regenera-
tion. A study provides evidence that bone marrow-derived c-kit+ cells can lead to
an improvement in cardiac function in mutant hypomorphic c-kit mice that is inde-
pendent of transdifferentiation into either cardiac muscle or endothelial cells, but
rather is associated with the release of angiogenic cytokines and associated neovas-
cularization in the infarct border zone (Fazel et al.
2006
). These findings suggest
the potential therapeutic effect of specific paracrine pathways for angiogenesis in
improving cardiac function in the injured heart.
A Critical Evaluation of Cell Therapy for Heart Disease
Cell therapy of heart diseases is promising but has not yet proven itself. Adequate
cell-based repair of adult myocardium remains a desirable goal but most cells that
are used cannot generate mature myocardium sufficient to promote large functional
improvements. ESCs can generate both mature cardiocytes and vasculature, but
their use is hampered by associated teratoma formation and the need for an alloge-
neic source. There is still difference of opinion among the cardiologists if the
therapy is ready to go into clinical practice. Several clinical trials of the bone
marrow-to-heart approach have been completed and some have shown positive
results. The overall degree of improvement in the patients' heart function has been
modest. The difficulties of the marrow-to-heart approach indicate that more
research is required.
The bone marrow stem cell technique appears to be reasonably safe because the
patients are injected with their own cells. Clinical trials are still in progress, for
example, at the Texas Heart Institute (Houston, TX). Earlier results were promising.
In 2004, two laboratories, one at Stanford University (Palo Alto, CA) and the other
at University of Washington (Seattle, WA) were unable to replicate the results claim-
ing transformation of bone marrow stem cells turn into heart tissue. The few that
lodged in the heart turned into blood cells in the usual way. According to the clini-
cians, the technique is safe as several hundred patients have now been treated world-
wide without adverse effect and the results so far are encouraging. Most studies,
however, show 5-10% improvement in heart function. This may be small but is
significant in view of the fact that most of the patients were very sick to start with.
The adult human heart as a source for cardiac stem cells is being further inves-
tigated. There is potential for autologous repair or even cardiac regeneration with
cells that follow a developmental pathway similar to embryonic cardiac precursors
but without the inherent limitations associated with undifferentiated ESCs.
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