Abstract
A new era has begun in the treatment of ischemic disease and heart failure. With the discovery that stem cells from diverse organs and tissues, including bone marrow, adipose tissue, umbilical cord blood, and vessel wall, have the potential to improve cardiac function beyond that of conventional pharmacological therapy comes a new field of research aiming at understanding the precise mechanisms of stem cell-mediated cardiac repair. Not only will it be important to determine the most efficacious cell population for cardiac repair, but also whether overlapping, common mechanisms exist. Increasing evidence suggests that one mechanism of action by which cells provide tissue protection and repair may involve paracrine factors, including cytokines and growth factors, released from transplanted stem cells into the surrounding tissue. These paracrine factors have the potential to directly modify the healing process in the heart, including neovascularization, cardiac myocyte apoptosis, inflammation, fibrosis, contractility, bioenergetics, and endogenous repair.
Highlights
Coronary artery disease accounts for two-thirds of heart failure cases in the United States [1], other causes leading to heart failure are due to non-ischemic events and include myocarditis, hypertension, diabetes, arrhythmias, valvular disease, hypothyroidism, and drug-induced cardiotoxicity
Pharmacological therapies for the treatment of heart failure have traditionally targeted pump function and quality of life for endstage heart failure patients, and several medications are available to limit the progression of the disease, the current therapies or interventional procedures do not lead to replacement of tissue and, do not stop or reverse progression of adverse left ventricular (LV) remodeling in all patients [2,3]
Fibrogenesis & Tissue Repair 2008, 1:4 http://www.fibrogenesis.com/content/1/1/4 aged myocardium, few studies have focused on paracrine factors released from these cells that may be involved in mediating cardiac repair
Summary
Paracrine factors from stem cells transplanted into the myocardium play an important role in modulating LV remodeling after an ischemic injury. Will it be important to determine which paracrine factors are up- or down-regulated, and to characterize the spatio-temporal release and the local concentrations produced by the injected or infused cell populations. An understanding of synergistic or additive interactions between these factors is crucial, as well as of whether these factors act on one or a combination of mechanisms that lead to heart failure. This may lead to the generation of pharmacological agents that can be used to treat heart failure, possibly negating the need for cell-based therapy altogether, (see Figure 1)
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