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J Am Coll Cardiol. 2017 Aug 8;70(6):728-741. doi: 10.1016/j.jacc.2017.06.010.

Fibrogenic Potential of PW1/Peg3 Expressing Cardiac Stem Cells.

Author information

1
Sorbonne-Universités, Université Pierre-et-Marie-Curie (UPMC), INSERM UMRS_1166, Institute of Cardiometabolism and Nutrition, Paris, France.
2
Sorbonne-Universités, UPMC, Plate forme d'Expérimentation Coeur Muscles Vaisseaux, Paris, France.
3
INSERM U1167, Université de Lille, Institut Pasteur de Lille, Fédération Hospitalo-Universitaire Remodeling in Valvulopathy and Heart Failure, Lille, France.
4
Sorbonne-Universités, Université Pierre-et-Marie-Curie (UPMC), INSERM UMRS_1166, Institute of Cardiometabolism and Nutrition, Paris, France. Electronic address: jean-sebastien.hulot@aphp.fr.

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 PW1nLacZ+/- 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

PMID:
28774379
DOI:
10.1016/j.jacc.2017.06.010
[Indexed for MEDLINE]
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