Personalized cardiac regeneration by stem cells-Hype or hope?

Abstract

Cardiac diseases are the leading cause of death and reach epidemic proportions with aging. Advanced heart disease results from an abrupt or progressive loss of contractile cardiomyocytes. Following percutaneous coronary intervention and revascularization regenerative medicine aims at effectively repair damaged tissue and replacement of lost cardiomyocytes. However, mixed results were obtained from trials using bone marrow-derived stem cells. Benefits were rather attributed to paracrine effects leading to inhibition or reverse of negative remodeling processes than to regeneration of viable cardiomyocytes. Thus the aim of regenerative medicine, in particular stem cell research, to generate viable cardiac muscle has so far not been achieved in humans, reflecting our incomplete understanding of underlying biological mechanisms. Moreover, there is growing evidence that substantial person-to-person differences in the outcome of stem cell therapy exists. We here review our present knowledge in evolving stem cell based cardiovascular medicine and highlight personalized aspects of stem cell interventions.

Fig. 1

Human stem cells and stem cell sources for cell-based functional repair after myocardial ischemia. Patient-specific autologous approach by reprogrammed induced pluripotent stem cells or multi- or monopotent adult stem cells compared to an allogenic approach using pluripotent embryonic stem cells is depicted. Stem cells from different sources can be expanded in vitro and differentiated into cardiovascular progenitor cells and mature cardiovascular cells (e.g. cardiomyocytes, red: α-actinin; endothelial cells, yellow: flt-1; smooth muscle cells, green: α-smooth muscle actin). Monopotent skeletal myoblasts proliferate and form multinucleated myotubes (myotube, green: titin). Following PCI for revascularization cells will be applied to the side of injury. Protocols in active randomized clinical trials are ongoing to address issues of optimal timing, dose and route of cell delivery. Abbreviations: PCI percutaneous coronary intervention, CSC cardiac stem cells; BMC bone marrow cell, EPC endothelial progenitor cell, MSC mesenchymal stem cell, SkM skeletal myoblast

Fig. 2

Stem cell triggered myocardial repair via cardioprotection and cardiomyocytes regeneration. Functional benefits obtained from trials using bone marrow-derived stem cells were rather attributed to trophic-paracrine effects (cardiprotection) leading to inhibition or reverse of negative remodeling processes than to regeneration of viable cardiomyocytes (cardiac regeneration)