Paracrine mechanisms of stem cell reparative and regenerative actions in the heart

Abstract

Stem cells play an important role in restoring cardiac function in the damaged heart. In order to mediate repair, stem cells need to replace injured tissue by differentiating into specialized cardiac cell lineages and/or manipulating the cell and molecular mechanisms governing repair. Despite early reports describing engraftment and successful regeneration of cardiac tissue in animal models of heart failure, these events appear to be infrequent and yield too few new cardiomyocytes to account for the degree of improved cardiac function observed. Instead, mounting evidence suggests that stem cell mediated repair takes place via the release of paracrine factors into the surrounding tissue that subsequently direct a number of restorative processes including myocardial protection, neovascularization, cardiac remodeling, and differentiation. The potential for diverse stem cell populations to moderate many of the same processes as well as key paracrine factors and molecular pathways involved in stem cell-mediated cardiac repair will be discussed in this review. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

Figure 1

Summary of stem cell-secreted paracrine factors. The proposed cardiac repair mechanisms these factor modulate include cell survival, neovascularization, remodeling, differentiation, contractility, and regeneration.

Figure 2

Autocrine/Paracrine mechanisms in cardiac repair. In response to environmental stimuli, stem cells release soluble factors that dynamically alter the myocardial microenvironment. These biologically active molecules exert effects on a variety of different cardiac cell types including the originating stem cells themselves. Paracrine actions of these factors lead to tissue protection, repair and regeneration while stem cell self-renewal and expansion is also regulated via autocrine feedback.