Stem cells for heart failure in the aging heart

Abstract

Despite a wide range of therapeutic interventions, the prognosis for most patients with heart failure remains poor. The identification of stem cells with the ability to generate cardiomyocytes and vascular cells and promote local repair and survival pathways has highlighted the ability of the heart to undergo regeneration and potentially provides a new therapeutic strategy for treatment of the failing heart. In recent years, however, clinical trials aimed at exploiting the beneficial effects of stem and progenitor cells to treat patients with cardiovascular disease have resulted in mild improvements at best, suggesting that these cells and/or the conditions in which they find themselves are not conducive to cardiac repair. Heart failure is most prevalent among older individuals, and a growing body of evidence suggests that with increasing age, cardiac stem and progenitor cells undergo senescent changes that impair their regenerative capacities. Moreover, environmental alterations over time appear to impact the capacity of these cells to improve cardiac function. Understanding these senescent changes may lead to the development of new and improved approaches to exploit the potential of stem cells to repair the aging heart. In this review, age-associated alterations in cardiac stem cell function are discussed, as well as strategies that are being investigated to promote cardiac regeneration in the patient with heart failure.

The Histone Methyltransferase Inhibitor BIX01294 Enhances the Cardiac Potential of Bone Marrow Cells

“…While successful stem cell interventions have been obtained using animal models [17,[79][80][81], as well as promising results in clinical trials on cardiac patients [82][83][84], the outcomes from these studies has not always been repeatable and has often been rather modest in effect [85,86]. It is not yet clear what the best sources are of stem cells for cardiac repair, and whether these various stem cell populations have been optimized in their cardiac capacity.…”

Human Embryonic and Fetal Mesenchymal Stem Cells Differentiate toward Three Different Cardiac Lineages in Contrast to Their Adult Counterparts

“…During embryonic development, stem cells contribute to organ formation, while later in life these cells or their derivatives are involved in repair and regeneration of organs [6]. However, with increasing age, the potential of stem cells declines [19], [20].…”

“…However, MSCs themselves are prone to the effects of aging and disease and if autologous MSCs are used, may suffer from decreased ability to proliferate, differentiate, home, engraft and exert immunosuppressive effects [4], [5]. Moreover, the developmental stage of tissues and different states of disease alter the microenvironmental regulation of stem cell behaviour [6]. Whether the developmental stage of MSC donor tissue also affects the cardiac differentiation potential of MSCs is not completely understood.…”

Aging Effects on Cardiac Progenitor Cell Physiology

“…Due to differential adhesion to immobilized ephrin A1, hCPCs with a younger phenotype are efficiently sorted, whereas p16 INK4a -positive old cells are selectively discarded (118). This constitutes a novel approach for enrichment of the pool of CPCs with higher regenerative potential, bearing clinical relevance, especially in the context of autologous stem cell transplantation in older patients (27,95,96). However, myocardial aging is a complex phenomenon dictated by a variety of genetic and environmental factors (50,83,127,209,298,345).…”