Biomedical Engineering Reference
In-Depth Information
There is a need for new heart valves, which it is estimated will be needed for
80,000 persons worldwide by the year 2020. Currently valves used for replace-
ments are obtained either from pigs or made artificially from metal, but they are not
as efficient or durable as human valves and wear out after 10-15 years. Heart
muscles could also be grown from stem cells in the laboratory, and would function
like the patient's own heart tissue. Adipose-derived stem cells (ADCs), which are
capable of differentiating into cells with phenotypic and functional features of
endothelial cells, are being investigated as a source of interstitial cells to populate
tissue-engineered heart valve constructs (Colazzo et al.
2010
).
ESC Transplantation for Tumor-Free Repair of the Heart
The propensity of ESCs for multilineage differentiation carries the liability of neo-
plastic growth, impeding therapeutic application. In one approach, the tumorigenic
threat associated with ESC transplantation was suppressed by cardiac-restricted
transgenic expression of the reprogramming cytokine TNF-a, enhancing the car-
diogenic competence of recipient heart (Behfar et al.
2007
). The in vivo aptitude of
TNF-a to promote cardiac differentiation was recapitulated in embryoid bodies
in vitro. The procardiogenic action required an intact endoderm and was mediated
by secreted cardioinductive signals. Researchers discovered approximately 15 pro-
teins whose production was dramatically increased after TNF-a stimulation. These
proteins, when combined into a cocktail, secured guided differentiation of ESCs,
producing cardiac progenitors called cardiopoietic cells, which are cardiac speci-
fied cell precursors rather than any cell type. Characterized by a downregulation of
oncogenic markers, upregulation, and nuclear translocation of cardiac transcription
factors, this predetermined population yielded functional cardiomyocyte progeny.
Such guided heart precursor cells did not form tumors, even though they were
transplanted at doses that would otherwise carry a high risk for tumorigenesis with
ESCs. Recruited cardiopoietic cells delivered in infarcted hearts generated cardio-
myocytes that proliferated into scar tissue, integrating with host myocardium for
tumor-free repair. Thus, cardiopoietic programming establishes a strategy to hone
stem cell pluripotency, offering a tumor-resistant approach for regeneration of the
heart after myocardial infarction.
Transplantation of Stem Cells for Acute Myocardial Infarction
Several stem cell technologies have been used for treatment of MI. Several of these
are in clinical trials.
Autologous Bone Marrow-Derived Stem Cell Therapeutics
The improvement in cardiac function after migration of autologous bone marrow-
derived stem cell (BMSCs) to the heart can be explained by their paracrine effects,
inducing angiogenesis and preventing ischemic myocardium from apoptosis
(Brunner et al.
2008
). These effects may explain why the number of circulating
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