Cell-based therapy has emerged as a promising approach to combat the myocyte loss and cardiac remodelling that characterize the progression of left ventricular dysfunction to heart failure. Several clinical trials conducted over the past decade have shown that a variety of autologous bone-marrow- and peripheral-blood-derived stem and progenitor cell populations can be safely administered to patients with ischaemic heart disease and yield modest improvements in cardiac function. Concurrently, rapid progress has been made at the pre-clinical level to identify novel therapeutic cell populations, delineate the mechanisms underlying cell-mediated cardiac repair and optimize cell-based approaches for clinical use. The following review summarizes the progress that has been made in this rapidly evolving field over the past decade and examines how our current understanding of the mechanisms involved in successful cardiac regeneration should direct future investigation in this area. Particular emphasis is placed on discussion of the general hypothesis that the benefits of cell therapy primarily result from stimulation of endogenous cardiac repair processes that have only recently been identified in the adult mammalian heart, rather than direct differentiation of exogenous cells. Continued scientific investigation in this area will guide the optimization of cell-based approaches for myocardial regeneration, with the ultimate goal of clinical implementation and substantial improvement in our ability to restore cardiac function in ischaemic heart disease patients.

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