Fibrogenic Potential of PW1/Peg3 Expressing Cardiac Stem Cells

Abstract

Background: Pw1 gene expression is a marker of adult stem cells in a wide range of tissues. PW1-expressing cells are detected in the heart but are not well characterized.

Objectives: The authors characterized cardiac PW1-expressing cells and their cell fate potentials in normal hearts and during cardiac remodeling following myocardial infarction (MI).

Methods: A human cardiac sample was obtained from a patient presenting with reduced left ventricular (LV) function following a recent MI. The authors used the PW1^nLacZ+/- reporter mouse to identify, track, isolate, and characterize PW1-expressing cells in the LV myocardium in normal and ischemic conditions 7 days after complete ligature of the left anterior descending coronary artery.

Results: In both human and mouse ischemic hearts, PW1 expression was found in cells that were mainly located in the infarct and border zones. Isolated cardiac resident PW1⁺ cells form colonies and have the potential to differentiate into multiple cardiac and mesenchymal lineages, with preferential differentiation into fibroblast-like cells but not into cardiomyocytes. Lineage-tracing experiments revealed that PW1⁺ cells differentiated into fibroblasts post-MI. Although the expression of c-Kit and PW1 showed little overlap in normal hearts, a marked increase in cells coexpressing both markers was observed in ischemic hearts (0.1 ± 0.0% in control vs. 5.7 ± 1.2% in MI; p < 0.001). In contrast to the small proportion of c-Kit⁺/PW1^- cells that showed cardiogenic potential, c-Kit⁺/PW1⁺ cells were fibrogenic.

Conclusions: This study demonstrated the existence of a novel population of resident adult cardiac stem cells expressing PW1⁺ and their involvement in fibrotic remodeling after MI.

Keywords: cardiac stem cells; fibrosis; ischemic cardiomyopathy; myocardial infarction.