Can we remove scar and fibrosis from adult human myocardium?

Abstract

The pathological processes leading to heart failure are characterized by the formation of fibrosis and scar, yet the dynamics of scar production and removal are incompletely understood. Spontaneous disappearance of myocardial collagen is reported in infancy but doubted in adulthood where scar volume constitutes a better prognostic indicator than the conventional parameters of ventricular function. Whilst certain drugs are known to attenuate myocardial fibrosis evidence is emerging that stem cell therapy also has the potential to reduce scar size and improve myocardial viability. Both animal studies and clinical trials support the concept that, as in infancy, cellular processes can be triggered to remove collagen and regenerate injured myocardium. The molecular mechanisms likely involve anti-fibrotic cytokines growth factors and matrix-metalloproteinases. Autologous cardiac, bone-marrow and adipose tissue derived stem cells have each shown efficacy. Specific immune privileged mesenchymal stem cells and genetically modified immunomodulatory progenitor cells may in turn provide an allogenic source for the paracrine effects. Thus autologous and allogenic cells both have the potential through paracrine action to reduce scar volume, boost angiogenesis and improve ventricular morphology. The potential benefit of myocardial cell therapy for routine treatment of heart failure is an area that requires further study.

Keywords: Cardiac stem cells; Heart failure; Ischaemic cardiomyopathy; Mesenchymal stromal cells; Myocardial scar; Regenerative medicine.