Advances in stem cell therapy for cardiovascular disease (Review)

Abstract

Cardiovascular disease constitutes the primary cause of mortality and morbidity worldwide, and represents a group of disorders associated with the loss of cardiac function. Despite considerable advances in the understanding of the pathologic mechanisms of the disease, the majority of the currently available therapies remain at best palliative, since the problem of cardiac tissue loss has not yet been addressed. Indeed, few therapeutic approaches offer direct tissue repair and regeneration, whereas the majority of treatment options aim to limit scar formation and adverse remodeling, while improving myocardial function. Of all the existing therapeutic approaches, the problem of cardiac tissue loss is addressed uniquely by heart transplantation. Nevertheless, alternative options, particularly stem cell therapy, has emerged as a novel and promising approach. This approach involves the transplantation of healthy and functional cells to promote the renewal of damaged cells and repair injured tissue. Bone marrow precursor cells were the first cell type used in clinical studies, and subsequently, preclinical and clinical investigations have been extended to the use of various populations of stem cells. This review addresses the present state of research as regards stem cell therapy for cardiovascular disease.

Figure 1

Spectrum of stem cells investigated for cardiac repair. Although the pathologic events leading to injured heart are multi-faceted, an underlying cause is a diminished blood supply to parts of the myocardium as a result of an occlusion to coronary artery. This translates into low, or no oxygen supply to the cardiac muscle leading to wide apoptosis and necrosis of the cells. As consequence, the heart cannot pump blood effectively to the rest of the body, thus leading to heart failure and ultimately death of the patient. The main purpose of stem cell therapies is the prevention and or regeneration of dying muscle. A variety of cell types have been investigated as candidates for such treatment. These cells include skeletal myoblasts, whole bone marrow cells or bone marrow-derived HSCs, bone marrow-derived MSCs, adipose-derived stem cells, adult cardiac resident stem cells, and ESCs including their differentiated progeny. The surface marker phenotypes that distinguish certain different stem cells are given in parentheses. HSCs, hematopoietic stem cells; MSCs, mesenchymal stem cells; ESCs, embryonic stem cells.

Figure 2

Potential therapeutic mechanisms of stem cells. Infusion of stem cells in the injured heart initiates myocardial repair via several direct and indirect mechanisms, including differentiation into cardiac and vascular cells, cell fusion and paracrine effects such as activation of endogenous precursors, promotion of neovascularisation, favorable modulation of the extracellular matrix, inhibition of apoptosis, and inhibition of hypertrophy. Collectively, these events result in enhanced LV function, improved perfusion, and improved cardiac function, leading to improvement in clinical status.