Abstract
Cells migrating from heart tissue biopsies during ex vivo culture have been associated with cardiomyogenic and angiogenic potential. We have characterized cells shed by murine cardiac explants cultured in MesenCult MSC medium. A relatively uniform population with a distinguishable morphology emerged from the early cellular outgrowth. This population expressed monocyte/macrophage and hematopoietic markers (CD11b+, CD14+, CD45+) but neither mesenchymal (CD90–, CD105–) nor endothelial (CD31–) markers. It was maintained in culture with a stable phenotype for more than 10 months. When cultured in differentiation medium, cells expressed cardiac sarcomeric α-actinin. They spontaneously formed sphere clusters (“cardiospheres”). This process was enhanced by TNFα. Spheres from neonatal mice exhibited spontaneous beating. To assess whether “contaminating” myocardial tissue fragments would explain CS beating, neonatal Z/EG transgenic mice were injected with an adeno-associated virus (AAV) vector expressing Cre-recombinase from a cardiac-specific promoter (Ncx1), resulting in the excision of a lacZ gene and activatation of the expression of the second reporter gene, enhanced green fluorescent protein (EGFP). Cardiac explants from Z/EG mice receiving AAV-9.Ncx1-CRE expressed EGFP, whereas the cellular outgrowth did not, demonstrating that the presence of cardiomyocytes in the outgrowth was not required for the generation of cardiac progenitor cells. Whether the myelo-monocytoid population originated from a retained hematologic component of explants or cardiac-resident leukocytes remains unclear. These results are in line with recent data on monocyte-derived multipotent cells (MOMC) with cardiomyogenic potential. They suggest that the cardiac-derived myelo-monocytoid cell, although not considered a classical adult progenitor cell, may have regenerative potential.
Highlights
Over the past decade, accumulating evidence has suggested that the adult mammalian heart may harbor one or more populations of progenitor cells endowed with regenerative potential [1]
Whether these cells represent adult cardiac-resident progenitor cells (CPCs) or bone marrow (BM)-derived cells homing to the heart is incompletely understood
The neonatal heart was rinsed abundantly with ice-cold heparinized saline and ventricles were cut into small pieces that were placed in Corning Costar 6-well plates (Sigma) with no extracellular matrix (ECM) protein coating
Summary
Over the past decade, accumulating evidence has suggested that the adult mammalian heart may harbor one or more populations of progenitor cells endowed with regenerative potential [1]. Whether these cells represent adult cardiac-resident progenitor cells (CPCs) or bone marrow (BM)-derived cells homing to the heart is incompletely understood. 5 seemingly different populations of cardiac stem cells have been described [4]. Whether these populations represent distinct entities of cardiac stem cells or different developmental and/or physiological stages of a single entity of stem cell remains unclear. No single cell surface marker definitely identifies a single entity of CPC
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