Contribution of Cardiac CD34⁺ Stromal Cells to Post-Myocardial Infarction Repair in Middle-Aged Rats

This study investigated the spatiotemporal dynamics of cardiac CD34⁺ stromal cells (SCs) during the reparative/proliferative phase of post-myocardial infarction (MI) healing. A transmural, non-reperfused MI was induced in middle-aged male Sprague-Dawley rats via left anterior coronary artery ligation, and proliferating cells were labeled with 5-bromo-2'-deoxyuridine. Hearts were collected at days 3, 7, and 14 after MI and analyzed using histology and immunohistochemistry. We found that the myocardial interstitium and coronary vessel adventitia harbored a population of cardiac CD34⁺ SCs. Following MI, activated CD34⁺ SCs expanded from the peri-infarct region across the healing wound through proliferation and migration, often alongside activated fibroblasts/myofibroblasts. While α-SMA⁺ myofibroblasts accumulated at pro-fibrotic granulation tissue sites, CD34⁺ SCs preferentially repopulated residual endomysial scaffolds spared by phagocytic macrophages. Over time, expanding fibrotic tissue progressively overtook these regions, leading to disappearance of CD34⁺ SCs. Importantly, clusters of CD34⁺ SCs accumulated at the scar border around the stumps of surviving cardiac myocytes, seemingly facilitating integration of endomysial connective tissue from non-infarcted myocardium into the developing fibrotic scar matrix. Collectively, these findings suggest that, unlike α-SMA⁺ myofibroblasts, cardiac CD34⁺ SCs seemed to support regenerative rather than fibrotic repair during post-MI wound healing by contributing to the preservation of myocardial stromal architecture.