Promises and pitfalls in cell replacement therapy for heart failure

Abstract

Symptomatic heart failure is a complex clinical syndrome with a poor prognosis. Many efforts have been made to develop new therapeutic strategies to improve prognosis associated with heart failure. In this context, different stem cell populations for cardiac regenerative therapy have been examined recently. Here we discuss the potential strategies for using stem cells in cardiac regenerative therapy and the barriers that remain before an effective cell-based cardiac regenerative therapy can be employed clinically.

Heart repair and regeneration: Recent insights from zebrafish studies

“…However, transplanting these cells has so far failed to significantly improve cardiac functions (measured as left ventricular ejection fraction), and any slight improvement in the test group was attributed to possible paracrine effects of the implanted cells . Cytokine and growth factor therapy is a promising noninvasive treatment for heart diseases and has been utilized to stimulate angiogenesis, to enhance cardiomyocyte proliferation and survival, and to recruit stem and progenitor cells to the damaged hearts . Fibroblast growth factor‐4 and vascular endothelial growth factor were among the first to be tested in clinical trials for revascularization.…”

“…Furthermore, several cytokines have been shown to mobilize bone marrow stem cells in animal MI models. Although initial clinical trials with granulocyte colony‐stimulating factor treatment were promising, subsequent double‐blinded trials did not show enhanced left ventricle ejection fraction or reduced infarct size . Tissue engineering approaches aim to create functional cardiac tissue implants with various combinations of cells and matrix scaffolds to replace damaged cardiac tissues.…”

“…Tissue engineering approaches aim to create functional cardiac tissue implants with various combinations of cells and matrix scaffolds to replace damaged cardiac tissues. However, there are still many technical challenges in this approach; for instance, one must decide which human cell types to use, what cell matrix to use as a scaffold, and how the engineered grafts can be vascularized such that they could reach the desired size . These considerations may also apply to stem cell or cytokine‐based approaches.…”

“…These considerations may also apply to stem cell or cytokine‐based approaches. Therefore, despite the recent progress on stem cells, cytokine and growth factor therapy, and tissue engineering, strategies for repairing diseased or injured hearts are still far from being able to regenerate a perfect heart. A more thorough understanding of the functional structure and the repair mechanism of cardiac tissues is required to improve current approaches in repairing and functional restoration of the injured heart.…”

Expression and reconstitution of the bioluminescent Ca2+ reporter aequorin in human embryonic stem cells, and exploration of the presence of functional IP3 and ryanodine receptors during the early stages of their differentiation into cardiomyocytes

“…Thus, although studies with animals have generated a lot of useful information regarding the development of the heart and the role of Ca 2+ signaling in this process, there is still a lot to discover about the development and regeneration of the human heart with respect to this essential second messenger. Research on human cardiomyocytes has progressed rapidly in recent years following the development of methods to generate cardiomyocytes from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) with the long-term strategy being that these cells might be applied in a clinical setting to treat heart disease (Krane et al, 2010;Kong et al, 2010;Poon et al, 2011).…”