Recent concepts for the roles of progenitor/stem cell niche in heart repair

Abstract

Progenitor/stem cell (PSC) has shown great promise for generation in failing heart. Advances in PSC biology have greatly enhanced our understanding of how PSC self-renewal, migration, maintenance of stemness, and cell-fate commitment depend on the balance of complex signals in their microenvironment. Endogenous PSC exists within structural and functional units known as PSC niches, which play important roles in directing PSC behavior. Recent years have witnessed great progress in our understanding of the PSC niche in cardiovascular biology. PSC based therapy could lead to successful cardiac regeneration or repair. Realizing the potential of therapeutic strategies is based on 1) differentiation of the PSC into all of the cellular constituents of the heart; 2) release of paracrine/ autocrine factors from the PSC; 3) fusion of the PSC with the existing constituents of the heart; and 4) stimulation of endogenous repair (regeneration of PSC niches). Importantly, cardiac PSC niches contain supporting cells and these cell-cell interactions have crucial regulatory roles in PSC based therapy. These findings have important implications for heart development, bioengineering, and furthermore elucidate a broader dimension of PSC control within the niche toward cardiomyocyte phenotype.

Keywords: Progenitor/stem cell; SDF-1α/CXCR4 axis; growth factors; myocardial infarction; progenitor/stem cell niches.

Figure 1

Schematic representation of stem cell niche. Niches are special microenvironments interacting with stem cells to regulate stem cell fate. Interactions between stem cells and adhesion molecules, extracellular matrix components, the oxygen tension, cytokines, and physiochemical nature of the environment including(PH, ionic strength etc.) are all coordinated to enforce quiescence (Green signals) and to tightly regulate self-renewal(White signals).

Figure 2

Stem cell homing mediated by upregulated SDF-1α can be seen as a model for communication between the injured heart and bone marrow. Endothelial cells of the blood vessels translocate SDF-1α from the damaged heart via the circulation into the bone marrow in a CXCR4-dependent manner. Presentation of the translocated SDF 1α by bone marrow endothelial and other stromal cells recruits CXCR4-expressing immature progenitors and stem cells as well as maturing leukocytes to the injured organ as part of host defense and organ repair.