Do Stem Cells Contribute to Heart Regeneration or Rather to Pathological Remodelling in Inflammatory Cardiomyopathy?

Understanding the pathways that chauffeur pathological remodelling in the failing heart still remains challenging. Myocardial inflammation is a common cause of pathological tissue remodelling in the heart promoting development of heart failures, often with the phenotype of inflammatory dilated cardiomyopathy. Pathological remodelling is associated with replacement of native cells by fibrotic tissue that reflects poor clinical prognosis and a stage of irreversibility. Substantial efforts have been attempted to develop therapeutic strategies aiming to regenerate the injured heart with stem cells. There is, however, increasing evidence that stem cells modulate inflammatory processes in damaged hearts acting in a paracrine fashion rather than directly regenerating cardiac tissue. The recent findings suggest that the poor effectiveness of stem-cellbased therapies in heart diseases is a result of the nonphysiological microenvironment of the affected cardiac tissue. In particular, the inflamed myocardium inhibits the cardio-regenerative capacity of transplanted stem cells, and instead promotes the pro-fibrotic processes. A growing body of evidence suggests that the specific signalling milieu of the affected heart is a key determinant of the fate and function of stem cells in the myocardium. Therefore, coupling the modulation of the myocardial microenvironment with patient-specific stem cells must be considered to achieve successful stemcell-based therapy in heart disorders. This review shortly summarises the current knowledge about the role of stem and progenitor cells in inflammatory cardiomyopathy and their potential use in stem-cell-based therapies.