Stem Cells for the Heart, Are We There Yet?

Abstract

Although several repair mechanisms have been described in the human heart, all fall too short to prevent clinical heart disease in most acute or chronic pathological cardiac conditions. Moreover, despite many breakthroughs in cardiovascular medicine, the complications of a myocardial infarction such as chronic heart failure remains a serious worldwide problem. Bone marrow stem cells could provide for a promising strategy to restore myocardial infarctions and prevent postinfarct congestive heart failure, because there is growing body of evidence that bone marrow stem cells, such as mesenchymal stem cells, can generate new cardiomyocytes in animals and humans. In this review, we will discuss important issues on stem cell therapy for cardiac regeneration after myocardial infarction, which might be of paramount importance when considering future human trials.

Quantitative imaging of myocardial infarct in rats with high resolution pinhole SPECT

“…Animal models of myocardial infarct have provided many clues to the underlying mechanisms of heart disease, and may be useful for preclinical evaluation of treatments such as new drugs, gene therapy [4], and stem cell implantation [5]. SPECT imaging of myocardial perfusion, with tracers such as [ 99m Tc]sestamibi, provides an accurate indicator of coronary artery disease, but only provided the data are quantitative, and are an accurate representation of the underlying state of the myocardium.…”

Autologous Stem Cells for Cardiac Repair: New Insights on Clinical Trial Safety and Best Cell Source

“…(Laflamme, et al, 2007 It remains unclear whether the beneficial effect results as a direct consequence of the transplanted cells participating and integrating in a functional syncytium with the host myocardium, or alternatively if the cells could benefit cardiac function without directly contributing to contraction (Dowell, et al, 2003). This indirect effect may be attributed to secretion of biologically active factors ) that could enhance the angiogenic process (Dowell, et al, 2003, Timmermans, et al, 2003, protect cardiomyocytes from apoptosis and induce proliferation, improve heart function with inotropic properties, or recruit resident cardiac stem cells . Implanted stem cells may also fuse with the native dysfunctional myocytes to augment function.…”

“…The immune system plays a crucial role during the acute phase of MI and this constitutes a most appropriate timing where any immunomodulatory effects following stem cell implantation could exert their effects (Laflamme, et al, 2007). An adequate microenvironment supporting nutrient delivery and waste removal is necessary to sustain survival, growth and possibly differentiation of the transplanted cells (Timmermans, et al, 2003). Therefore, concurrent revascularization must keep pace with cell repopulation of the infarcted tissue (Luttun and Carmeliet, 2003).…”

“…Importantly, an angiogenic response has been observed in many studies following cell transplantation (Dowell, et al, 2003). Much attention has been focused on the direct consequence of cell-based therapy by the renewal of lost parenchymal cells, but restoration of the extra-cellular matrix and vascular supply are also important issues since both components are essential for structural and functional support of the surviving cardiomyocytes (Timmermans, et al, 2003) in the ischemic myocardium. It is also important to consider other potential mechanisms by which transplanted cells could benefit cardiac function without directly contributing to systolic contraction.…”

“…Some reports have suggested that MSC implantation into ischemic tissue promote collaterals development through paracrine mechanisms, but not through direct cell incorporation into growing vasculature (Dowell, et al, 2003, Fuchs, et al, 2001, Hirata, et al, 2003, Kamihata, et al, 2001, Kinnaird, et al, 2003, Kobayashi, et al, 2000, Mangi, et al, 2003, Strauer, et al, 2002. MSC express genes encoding a broad spectrum of cytokines with angiogenic properties including VEGF, HGF, FGF, MCP-1, PGF, IL-1 and IL-6, SDF-1, MMP-9 , Timmermans, et al, 2003 shown to have positive effects on experimental blood flow recovery (Buschmann, et al, 2003, Timmermans, et al, 2003. Moreover, media collected from MSC cultures (MSC-derived conditioned medium, MSC-CM) promote in vitro proliferation and migration of endothelial cells (EC) and vascular smooth muscle cells (VSMC), and enhance in vivo collateral blood flow recovery when injected into ischemic hindlimb , Timmermans, et al, 2003.…”