Abstract
Cardiac damage is one of major cause of worldwide morbidity and mortality. Despite the development in pharmacotherapy, cardiosurgery and interventional cardiology, many patients remain at increased risk of developing adverse cardiac remodeling. An alternative treatment approach is the application of stem cells. Mesenchymal stem cells are among the most promising cell types usable for cardiac regeneration. Their homing to the damaged area, differentiation into cardiomyocytes, paracrine and/or immunomodulatory effect on cardiac tissue was investigated extensively. Despite promising preclinical reports, clinical trials on human patients are not convincing. Meta-analyses of these trials open many questions and show that routine clinical application of mesenchymal stem cells as a cardiac treatment may be not as helpful as expected. This review summarizes contemporary knowledge about mesenchymal stem cells role in cardiac tissue repair and discusses the problems and perspectives of this experimental therapeutical approach.
Highlights
Cardiac diseases remain a major cause of worldwide morbidity and mortality[1]
Conditioned media from mesenchymal stem cells (MSCs) can protect CMCs from apoptosis when it inhibits caspase-3 activation and the release of cytochrome C from the mitochondria. These findings suggest that MSCs paracrine signalling helps to protect CMCs by interfering with mitochondria-mediated apoptotic pathway[56]
This study further demonstrates that MSCs can differentiate into CMCs in various extent when nearly 25% of green fluorescent protein (GFP)-MSCs express one of two cardiomyocyte markers in the absence of MSCs characteristics
Summary
Cardiac diseases remain a major cause of worldwide morbidity and mortality[1]. In the United States of America every 34 seconds somebody suffers a coronary event[2]. Aged MSCs have lower differentiation ability and proliferation potential[46,47] and the age related loss of regenerative potential of MSCs is even dependent on the source of MSCs (ref.[47]) Based on both in vitro and in vivo studies, three main mechanisms of action of MSCs implementation in cardiac tissue reparation process are suggested – differentiation into functional cardiomyocytes (CMCs), paracrine and immunomodulatory effect (Fig. 1). In MI rat model, injected MSCs increased levels of angiogenic factors FGF-2, VEGF and stem cell homing factor (SDF-1α) in infarcted hearts This was followed by declined CMCs apoptosis, increased capillary density and improved left ventricular contractility[68]. In PROMETHEUS, the clinical trial where autologous bone marrow MSCs were injected into infarcted site of myocardium of 6 patients not eligible for bypass surgery, it was shown that MSCs reduce scar mass size for 48%
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