Over the past decades, substantial advances in risk factor modification, pharmacological treatment, and revascularisation therapy have significantly reduced the mortality of ischaemic heart disease (IHD). Nevertheless, IHD remains a leading cause of morbidity and mortality. Cell therapy is currently being investigated as a potential treatment modality for patients with IHD. Preclinical studies suggested that cell therapy may have a favourable effect on tissue perfusion and contractile performance by promoting vascularisation and myocyte formation. Following these encouraging preclinical results, cell therapy has rapidly been introduced into the clinical setting.

This paper aims to provide an overview of the basic principles of cardiac cell therapy. First, the potential mechanisms through which cell therapy may improve cardiac performance and the different cell populations that have been tested in preclinical studies are discussed. Thereafter, the different routes of cell delivery are reviewed, along with the results of the currently available clinical studies investigating the safety, feasibility and efficacy of cardiac cell therapy for patients with IHD.

POTENTIAL MECHANISMS THROUGH WHICH CELL THERAPY MAY IMPROVE CARDIAC PERFORMANCE

Originally, cell therapy was thought to improve cardiac performance through transdifferentiation of the injected cells into cardiomyocytes. Although several early studies supported the ability of cell therapy to regenerate cardiomyocytes,1 ^w1 subsequent studies failed to support these initial observations.^w2–4 Since then, it has become apparent that the mechanistic underpinnings of cardiac cell therapy appear to be far more complex (fig 1). Several groups offered fusion of donor cells with host cardiomyocytes as an explanation for previous claims of transdifferentiation.^{w4 w5} Others reported that cell therapy may promote vascularisation by physical incorporation of the injected cells into new capillaries or in perivascular cells.2 ^w6 Still, the discrepancy between the massive cell death occurring within 24 h after cell transfer and the sustained functional improvement shown by many groups suggest that other mechanisms may be involved. …