Chapter 68. Cell Therapy for Cardiovascular Diseases
Which of the following is not a proven mechanism for cell therapy–mediated cardiovascular repair and regeneration?
A. Differentiation or transdifferentiation into new cardiac or vascular cells
B. Secretion of growth factors and cytokines that promote vasculogenesis and prevent apoptosis
C. Stimulation of endogenous cardiac precursor cells
D. Entire organogenesis from injected stem cells
Mechanisms by which cell therapy leads to cardiovascular repair and regeneration remain a subject of controversy. Although differentiation or transdifferentiation into new cardiac or vascular cells was initially believed to be the primary mechanism, recent studies suggest that stimulation of endogenous precursor cells, secretion of growth factors and cytokines (paracrine effect) that promote vasculogenesis and prevent apoptosis, or rarely, fusion of donor cells with host cells may be potential mechanisms. Together, these cellular changes result in enhanced perfusion, reduced infarct size, improved left ventricular remodeling, and ultimately improved cardiac function and patient mortality. Entire organs are not formed from administered stem cells. Most of the regenerated tissue is formed from endogenous cells.
Which of the following cellular delivery mechanisms results in the highest retention of delivered cells to the myocardium?
A. Intracoronary arterial administration to areas of interest with intermittent balloon catheter inflation (stop-flow)
B. Intravenous injection into a peripheral vein
C. Direct intramyocardial injection using open surgical or catheter-based approaches
D. Engineered monolayer tissue transplantation
Intravenous infusion of stem cells is associated with the lowest rates of myocardial cell retention as the majority of intravenous infused cells become trapped in the pulmonary, hepatic, and splenic microvasculature. Intracoronary infusion circumvents the pulmonary and hepatic first-pass effect by delivering cells directly into target areas of myocardium. When delivered using a stop-flow method with intermittent balloon arterial occlusion, there is increased homing to the supplied areas. However, infusion of larger mesenchymal stem cells has been associated with embolization of the microvasculature. Although more invasive and associated with a greater risk of myocardial perforation, transendocardial injection leads to the greatest rates of cell delivery and retention, especially when used in conjunction with electromagnetic mapping catheter systems. Although promising, the use of engineered monolayer tissue transplantation has not been studied in human subjects.
The injection of which stem cell type has been associated with increased risk of ventricular arrhythmias?