Stem-cell therapy for cardiac disease

Abstract

Heart failure is the leading cause of death worldwide, and current therapies only delay progression of the disease. Laboratory experiments and recent clinical trials suggest that cell-based therapies can improve cardiac function, and the implications of this for cardiac regeneration are causing great excitement. Bone-marrow-derived progenitor cells and other progenitor cells can differentiate into vascular cell types, restoring blood flow. More recently, resident cardiac stem cells have been shown to differentiate into multiple cell types present in the heart, including cardiac muscle cells, indicating that the heart is not terminally differentiated. These new findings have stimulated optimism that the progression of heart failure can be prevented or even reversed with cell-based therapy.

Transplantation of Adipose Tissue-Derived Stem Cells Overexpressing Heme Oxygenase-1 Improves Functions and Remodeling of Infarcted Myocardium in Rabbits

“…Cellular cardiomyoplasty, which seek to replace or regenerate cardiomyocytes through cell transplantation, may be achieved in several ways, at least including transplanting stem cells that differentiate into cardiomyocytes or promote angiogenesis (Segers and Lee 2008), protecting cardiomyocytes as well as vascular endothelial cells via a paracrine mechanism (Takahashi et al 2006) and mobilizing autologous resident stem cells to the site of injury by using cytokines (Zhao et al 2009). Furthermore, electrophysiological stabilization and neural structure, referring to as gap junction and nerve sprouting respectively, are indispensable for evaluating effects and safety of cellular therapy in heart disease, especially in large animal and in humans (Cai et al 2009).…”

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration

“…Thus, there has been great interest in novel therapeutic options, such as gene (reviewed in [2]) and stem cell therapy (reviewed in [3]), or even direct administration of proangiogenic cytokines [4]. In the case of growth factor-based therapy, although preclinical studies and initial clinical trials had suggested beneficial effects [5,6], doubleblinded clinical trials with large cohorts of patients failed to validate the efficacy [7][8][9].…”

Cell-based cardiovascular repair and regeneration in acute myocardial infarction and chronic ischemic cardiomyopathy current status and future developments

“…Embryonic stem cells are undifferentiated, pluripotent cells obtained from the inner cell mass of blastocysts that have the most promising potential for organ regeneration (Segers et al 2008;Smith 2001). Their unlimited capacity for differentiation has gained incremental interest for their use in regenerative cardiology.…”

“…Experimental and first small-to intermediate scale clinical studies have suggested the feasibility and safety of cell-based therapies in patients with ischemic cardiomyopathy (Landmesser 2009;Segers et al 2008). Heterogeneous cell populations have been thoroughly investigated as potential sources of cardiac progenitors in cell based therapy for ischemic heart disease.…”

“…Despite improved pharmacological therapy and coronary revascularization procedures by either percutaneous coronary intervention PCI or coronary artery bypass surgery CABG there is still a major need for novel therapeutic approaches (Landmesser et al 2005); (Ford et al 2007). Whereas current treatment strategies aim largely to limit or delay progression of cardiac dysfunction (Landmesser et al 2005;Landmesser et al 2009;Segers et al 2008) stimulation of vascular and cardiac repair mechanisms, such as those mediated by stem/progenitor cells, has become an important focus of cardiovascular research (Landmesser 2009). In fact, in patients with ischemic heart failure it is unlikely that the inhibition of novel neurohormonones other than catecholamines, angiotensin and aldosterone will further improve cardiovascular outcome, underlining the need for novel therapeutic concepts to promote cardiac repair (Landmesser et al 2009).…”