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 self-renewing, 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.

Figure 1

a: Confocal analysis of human cardiospheres derived from percutaneous endomyocardial biopsy specimens. Expression of cytoplasmic cardiac markers are shown: cardiac myosin heavy chain (cMHC, red) and cardiac troponin I (cTnI, green). Expression of stem cell and mesenchymal markers are shown: c-Kit (red) and CD105 (green). b: c-Kit and CD105 expression are maintained after cardiosphere expansion as shown by example flow cytometric histograms. c: c-Kit expression demonstrated by western blot analysis for two different patients. Positive control (CTR+) and negative control (CTR−) were performed using the c-Kit–positive cell line TF1 and the c-Kit-negative cell line MCF7, respectively. CDCs = cardiosphere-derived cells; CSps = cardiospheres.

Figure 2

a: Left ventricular ejection fractions (LVEF) in the three experimental groups (control group summarizes phosphate buffered saline (PBS)-injected group and fibroblast-injected group) 3 weeks after myocardial infarction was created and cells were injected. *P <.01. b, c: Representative Masson trichrome-stained sections from infarcted hearts, explanted 3 weeks after injection of cardiosphere-derived cells (b) or PBS (c). CDCs = cardiosphere-derived cells.