Biomedical Engineering Reference
In-Depth Information
improving the damaged myocardium secondary to ischemia have been well
documented.
Initial clinical trials have shown the efficacy of autologous skeletal myoblast
transplantation in patients with left ventricular (LV) dysfunction. The use of skeletal
myoblasts delivered by multiple intramyocardial injections was effective in restoring
LV function in a genetically determined Syrian hamster model of dilated cardio-
myopathy, demonstrating that the functional benefits of transplanted skeletal myo-
blast can be extended to nonischemic cardiomyopathy.
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12.2.1 Advantages to Myoblast Transplantation
Because myoblasts can be of autologous origin and can be robustly expanded in
culture, a large number of cells can be obtained from only a small skeletal muscle
biopsy sample in a relatively short period of time. Compared with transplanted
cardiomyocytes, myoblast cells appear to be more resistant to ongoing apoptotic
damage, which tends to be prevalent at ischemic sites. Skeletal myoblasts were the
first cells to be tried for cell-based cardiac therapy. They do not form tumors as with
ESCs. Moreover, they can be easily handled and expanded in vitro (millions of
myoblasts can be grown from a single muscle biopsy within a relatively short time).
Myoblasts after injection into the infarcted heart have been shown to exhibit long-
term engraftment;
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.
12.2.2 Disadvantages with Skeletal Myoblasts
Skeletal myoblasts do not adopt a cardiomyogenic differentiation .Moreover, they
lack gap junctions, have not been shown to integrate electromechanically with the
surrounding myocardium. They do not beat in synchrony and are isolated from the
rest of the myocardium. Clinical trials of myoblast therapy have shown improve-
ments in ejection fraction that persist 10 months following injection.
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12.2.3 Further Recommendations
Although preclinical studies with stem cell and myoblast transplantation have shown
similar levels of efficacy, there is a need for a detailed evaluation on the relative
benefits, adverse effects, and efficiency of skeletal myoblast and stem cell transplants
in the clinical setting (e.g., heart failure) vis a vis the restoration of myocardial
function. New methods to better assess and optimize posttransplanted myoblast
recruitment and survival, particularly in the long term, need to be developed, and the
repertoire of effective, less invasive cell delivery technologies needs to be expanded.
12.3 ADULT BONE MARROW-DERIVED STEM CELLS
The bone marrow contains a varied assortment of progenitor cells, including
hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), multipotent
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