Endogenous Cardiac Stem Cell Therapy for Ischemic Heart Failure

Abstract

Cardiovascular disease remains the number one cause of morbidity and mortality in the world. With great advances in medical and interventional therapies, patients who suffer from acute myocardial infarction have a longer life expectancy than before, but gradually develop chronic heart failure in their later life due to irreversible loss of cardiomyocytes. So far, heart transplantation is the only therapeutic option for advanced heart failure. However, the shortage of donor organs largely limits its role as the gold standard therapy. In the past decades, stem cell-based regenerative medicine has been proposed as a promising approach for the treatment of heart failure based on numerous animal studies. A variety of potential stem cell types, including skeletal myoblasts and bone marrowderived stem cells, have been investigated in clinical trials for cardiac repair and regeneration, but have shown mixed results in heart functional improvement or life-threatening disadvantages such as ventricular arrhythmia. On the other hand, due to the advantages of autologous origin and cardiac-committed lineage, cardiac stem cell therapy has emerged as a promising cell-based strategy for treatment of HF. Thus, this review discusses the current therapies for heart failure and further focuses on stem cell therapy using different endogenous cardiac stem cells, purified by stem cell surface markers (e.g., c-kit or Sca-1) or derived from explants via the formation of cardiospheres. In addition, the potential effect of patient age on cell-based therapy for heart disease is discussed.

Challenges in identifying the best source of stem cells for cardiac regeneration therapy

“…Secondly, these cells could be successfully administered by intracoronary injection to patients with prior MI [ 67 , 69 , 71 ]. For autologous transplantations, CSCs are usually isolated from atrial appendages and ventricular and epicardial biopsies [ 72 ]. However, since atrial and ventricular cardiomyocytes have differential gene expression and functional efficacy, it is not known whether the stem cells from atria and ventricles have the same characteristics and functions [ 73 ].…”

Collagen type I and hyaluronic acid based hybrid scaffolds for heart valve tissue engineering

“…N ‐(3‐dimethylaminopropyl)‐ N ′‐ethylcarbodiimide hydrochloride (EDC)/ N ‐hydroxysuccinimide (NHS) crosslinking route also offers advantages such as zero‐length crosslinks, preservation of triple helix structure, close control over reaction conditions, and water‐soluble by‐products . Moreover, cardiosphere‐derived cells (CDCs), selected in this study, are an endogenous population present in the adult heart with differentiation affinity into myocytes, smooth muscle cells, and endothelial cells (EC) . Their therapeutic efficacy has been established in animal models and a clinical trial reported reduced area of damage in CDC‐treated patients …”

“…[28,29] Moreover, cardiosphere-derived cells (CDCs), selected in this study, are an endogenous population present in the adult heart with differentiation affinity into myocytes, smooth muscle cells, and endothelial cells (EC). [30,31] Their therapeutic efficacy has been established in animal models [32,33] and a clinical trial reported reduced area of damage in CDC-treated patients. [34,35] In this study, it has been hypothesized that heterogeneous hybrid scaffolds with varying crosslinking densities could be developed using a multistep sequential crosslinking technique based on EDC/NHS.…”

Murine Cardiosphere-Derived Cells Are Impaired by Age but Not by Cardiac Dystrophic Dysfunction

“…Cardiac stem cells (CSCs), identified in the heart in 2003 [2,3], are primed to repair damaged myocardium, but are able to replace only a small proportion of the cells in the heart per year [4][5][6]. To provide sufficient cells for therapy, CSCs can be expanded in vitro, after selection using cell surface markers, such as c-kit [3] or Sca-1 [2], or from explanted biopsies via the formation of cardiospheres [7,8].…”