Biomedical Engineering Reference
In-Depth Information
or antiapoptotic responses in the myocardium. These cell engineering techniques
might also allow the specific targeting of mitochondrial-based cytopathies. To
identify aspects of the cardiac milieu that may contribute to the growth and
development of transplanted myoblasts in vivo, 3-dimensional matrices have
been designed to serve as a novel in vitro system that mimic some aspects of the
electrical and biochemical environment of the native myocardium. These structures
may allow a finer resolution of electrical and biochemical signals that may be
involved in myoblast proliferation and plasticity. Myoblasts have been grown on 3D
polyglycolic acid mesh scaffolds under controlled conditions in the presence of
cardiac-like electrical current fluxes and in the presence of culture medium that had
been conditioned by mature cardiomyocytes. Such scaffolds containing either fetal
or neonatal aggregates of contracting cardiac cells have been used to generate
artificial cardiac grafts transplanted into injured myocardium with recuperation of
ventricular function and formation of functional gap junctions between the grafted
cells and the myocardium (Table 12.9).
The combination of gene therapy and stem cell engineering is an attractive
approach for treating cardiac disorders. Overexpression (and in some cases, inhibi-
tion of expression) of specific proteins can result in striking changes in cardiomyo-
cytes and in cardiac phenotype. Specific cardiomyocyte functions, including ion
channel, cardiac conduction, contractility, and myocyte proliferation, have been
shown to be effected by the gene transfer and expression of specific proteins. Cell-
based therapies for injured or dysfunctional hearts can be enhanced by the use of
ex vivo genetically modified stem cells to deliver genes and proteins. For instance,
transplanted MSCs have been shown to be effective devices to deliver channel
proteins involved in pacemaking activity (e.g., channel protein HCN2), resulting in
the modification of cardiac rhythm in vivo.
35,126,141-143
Several open questions are likely to be answered in the future:
1. What is the optimal time of delivery after acute myocardial infarction?
2. Is there a dose-response relationship?
3. How do different cell types compare?
4. The mechanism by which stem and progenitor cells achieve a functional
improvement, which is difficult to test in the clinical scenario. In chronic
ischemic HF, a superimposed question is whether identifying hibernating
myocardium to direct cell therapy is essential to an effective outcome. The
treatment for nonischemic heart disease is not yet addressed.
12.6.4 New Method Helps Stem Cells Find Damaged Tissue Better
Because the ability of stem cells migrating to damaged areas is well known, stem
cells also have the ability to detect proteins that are secreted from the damaged tissue.
Stem cells are chemotactic to detect movement (as amoeba, white blood cells
attracted to chemicals and the movement around it). Research teams compared stem
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