Stem cells in the heart: What's the buzz all about?—Part 1: Preclinical considerations

Abstract

New approaches for cardiac repair have been enabled by the discovery that the heart contains its own reservoir of stem cells. These cells are positive for various stem/progenitor cell markers, are selfrenewing, and exhibit multilineage differentiation potential. Recently we developed a method for ex vivo expansion of cardiac-derived stem cells from human myocardial biopsies with a view to subsequent autologous transplantation for myocardial regeneration. Here we review the state of the cardiac stem cell field and our own work on cardiosphere-derived stem cells from human hearts. The first of this two-part review outlines emerging preclinical data on the application of cardiac stem cells. Part 2 continues with a discussion of other stem cell sources with clinical potential, a summary of the critical issues surrounding stem cell therapy (with an emphasis on the crucial issue of how cell transplantation may influence arrhythmias), our perception of clinical stem cell trials to date, and the issues facing the clinical application of cardiac stem cells.

Stem Cell Therapy for Myocardial Infarction: Are We Missing Time?

“…Knowledge on timing stem cell therapy could therefore have vast consequences for further stem cell research and clinical applications when the time it takes to prepare the treatment exceeds the window of opportunity. Harvesting, culturing, and transplanting autologous cardiac stem cells takes at least 3 weeks [1] and, although these techniques show progress, this might be longer than wished for. Similarly, creating induced pluripotent stem cells through the reprogramming of somatic cells takes approximately 3–4 weeks [60].…”

“…Experimental studies investigating different kinds of stem and progenitor cells in animal models of MI have shown promising results obtained with cardiac stem cells [1], embryonic stem cells [2,3], skeletal myoblasts [4], and bone-marrow-derived stem cells (BMSCs) [5,6,7], although skeletal myoblasts have later been shown to be arrythmogenic [8] and when further investigating this cell line extreme caution should be in place. While much of the research is still in the preclinical phase, BMSC therapy after MI was shown to be successful in a recent systematic review of clinical trials [9].…”

Cellular and Molecular Characterization of Human Cardiac Stem Cells Reveals Key Features Essential for Their Function and Safety

“…All CSCs populations contain most properties of stem cells: self-renewal, multi-lineage differentiation, and clonogenic potentials. CSCs can improve heart function after transplantation [9].…”

Endomyocardial biopsy derived adherent proliferating cells—A potential cell source for cardiac tissue engineering

“…Among these, cells expressing stem cell factor receptor c-Kit (CD117) [Beltrami et al, 2003], stem cell antigen-1 (Sca1) [Oh et al, 2003], and homeodomain transcription factor islet-1 (Isl1) [Laugwitz et al, 2005], SP cells [Pfister et al, 2005], and cells able to grow in cardiospheres [Messina et al, 2004] have been suggested to be capable of differentiation into cardiomyocytes, either in vivo or in vitro. Several studies are ongoing, but a clinically feasible method for isolating and expanding human CSC for application during an injury event is still lacking [Smith et al, 2008].…”