Douglas W. Losordo, MD [ View bio ] (Northwestern University, Chicago, IL)
As the population ages and the acute mortality from cardiovascular disease decreases, a large population of patients is emerging who have symptomatic chronic ischemic cardiac and vascular disease, many of whom remain severely symptomatic despite exhausting conventional medical therapy and mechanical revascularization. Mounting evidence suggests that microvascular insufficiency plays a significant role in the pathophysiology of ischemia. Recognizing this problem, investigators have worked to understand the biology of the vascular system and harness this information to develop new treatments for patients with ischemic diseases. With this end in mind, the science of therapeutic angiogenesis has been evolving for over two decades.
Preclinical and early clinical data provide evidence that a variety of growth factors and stem/progenitor cells may be employed therapeutically for repair of ischemic tissue. Preclinical studies have provided evidence for safety and the potential therapeutic potency of endothelial progenitor cells, both as cultured and freshly isolated cells. Early phase clinical trials using a variety of approaches have been completed providing data supporting the feasibility, safety and bioactivity of EPCs for treatment of advanced cardiovascular disease. Pivotal trials are under way. Accordingly, the goal of ischemic tissue repair appears feasible and is being approached in human clinical trials.
The evolution of the strategy of ischemic tissue repair will require an ongoing dialogue between clinicians, scientists, regulators and industry to take full advantage of advances in our understanding of the biology of these processes and thereby drive their appropriate application to patients.
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