Atrial Appendage-Derived Cardiac Micrografts: An Emerging Cellular Therapy for Heart Failure

Cells capable of cardiomyocyte-like differentiation have been in the limelight for several years. Such cells have been investigated extensively for their potential to regenerate the injured heart when transplanted. The heart’s capacity for repair is limited, although some degree of cardiomyocyte regeneration has been shown to occur throughout adulthood. However, the elusive nature of adult cardiac stem cells has led to inconclusive evidence of their presence. Direct replacement and delivery of electrically active, contractile cells to the heart are presented with further challenges related to electrical coupling and arrhythmias. Furthermore, cell types with stem or progenitor characteristics require extensive manipulation, enrichment, and expansion before their use as therapy. As tissue regeneration is a finely orchestrated interplay of several cell types, it has not been surprising that combining cardiomyocyte-like cells with endothelial or mesenchymal cells has shown promise over therapy using cells of a single type. An alternative mechanism to direct replacement of cardiomyocytes lost to, for example ischemic damage, is the stimulation of the myocardium’s inherent protective capacities and pathways for functional repair. This is achievable by several means, including drugs, biomaterials, and cells or their released soluble factors. In these approaches, the challenges lie in targeted delivery and the long-term efficacy of the therapies. A recent advance in functional cardiac repair is the utilization of an individual’s autologous, processed cardiac micrografts derived from atrial appendages. The atrial appendages are pouch-shaped annexes of the atria. For example, the left atrial appendage can contribute to the formation of blood clots, especially during atrial fibrillation, which is the rationale for its clinical closure or even excision in some cases. Hence, atrial appendage excision is an attractive strategy to obtain cardiac tissue safely and directly from the patient. Micrograft transplants produced from cardiac atrial appendages comprehensively harbor most myocardial cell types intricately meshed with their supporting extracellular matrix. The atrial microtissue transplants produce paracrine factors, such as atrial natriuretic peptides, which, from a therapeutic viewpoint, have been elucidated to convey both antifibrotic and cardioprotective effects on the myocardium. Their targeted delivery is achievable upon open heart surgery by epicardial transplantation, and they are apt targets for gene therapy applications. This chapter provides insight into the current state of autologous cardiac micrografts and micrograft therapy, its proposed mechanisms of action, and means of processing for transplantation during cardiac surgery.