Composition of Bone Marrow‐Derived Progenitor Cells in the Cellular Infiltrate of Infarcted Hearts: Role of Local Oxygen Tension

Abstract

Our objective was to determine the origin and phenotypes of cells in the early mononuclear infiltrate of infarcted hearts. Methods. In mice transplanted with bone marrow from LacZ-expressing donors, we performed (a) permanent coronary ligation (n=5), or (b) ligation for 30 min, followed by release (n=5). These mice, and (c) sham-operated controls, were sacrificed after 7 days. The cellular composition in the hearts was assessed by immunocytochemistry, after staining for beta-galactosidase expression. Using a novel in vivo EPR oximetry method, we also measured the time course of oxygenation of the infarcted hearts. Results. In the infarcted areas, we found a mosaic distribution of the following markers: LacZ (bone marrow origin); F4/80 (macrophages); smooth muscle alpha actin; troponin I (in mononuclear cells located mainly in the border zone), and ABC-G2 (‘side population’ progenitors). At the core of infarcted territory we noted a paucity of organized microvessels, indicating a state of chronic ischemia. This was confirmed by the dramatic decrease in the local, EPR-detectable oxygen tension. Re-vascularized hearts displayed only minimal, focally distributed damage. Conclusion. At one week post-infarction, we detected bone marrow derived progenitor cells with phenotypes topographically correlated to the pattern of oxygenation. This finding advocates for the potential benefit of post-infarct re-vascularization therapy.