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Stem cell therapy has attracted considerable interest in the treatment of cardiovascular disorders. This is driven by the observation that the heart’s regenerative capacity is insufficient to recover from ischemia or other cardiotoxic insults and the progressive nature of tissue ischemia in patients with coronary artery disease or peripheral arterial disease (PAD). Directed homing of bone marrow–derived stem cells after myocardial injury produced functional improvements in animal studies,1,2 leading to the hypothesis that enhancing mobilization of bone marrow stem cells or their direct delivery can result in clinical improvement in acute or chronic cardiac injury. Similarly, evidence supporting the incorporation of circulating and bone marrow–derived progenitor cells into newly formed vasculature in limb ischemia models supported the premise that enhanced progenitor cell delivery can reverse tissue ischemia.3,4
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Improvements in our understanding of stem cell biology, cardiac differentiation, and response to cardiovascular injury have advanced the field of cardiac cell therapy.5,6 These findings have led to numerous studies investigating the efficacy of multiple bone marrow stem cell lineages and other stem cell sources on cardiovascular recovery. To date, no stem cell therapy is approved by the Food and Drug Administration for a cardiovascular indication, but the growing body of literature provides a promising signal to encourage multiple Phase III clinical trials. This chapter will examine the clinical experience and potential applications of stem cell therapy by reviewing each stem cell lineage (Table 10–1).
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MECHANISMS UNDERLYING STEM CELL THERAPY
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There are multiple mechanisms by which stem cells may exert a beneficial effect in the cardiovascular system (Fig. 10–1), but some common themes are important to highlight. First, the mechanism by which any stem cell lineage exerts a potential benefit in humans is not yet fully explained. Second, the inability to track stem cells or perform histopathological studies in human subjects impairs the ...