CD34+ Stromal Cell/Telocytes Demonstrate a Dynamic Pattern of Distribution During Healing of Post-Infarcted Myocardium in Middle-Aged Sprague-Dawley Rats

Abstract

Introduction: Myocardial CD34+ stromal cells/telocytes (SC/TCs) have been recently recognized as a novel resident cell which may play an important role in the repair process following acute myocardial infarction (MI). This study aims to determine the spatiotemporal dynamics of CD34+ SC/TCs within the left ventricular (LV) wall during the late inflammatory and proliferative phases of post-MI scar formation. Methods: A large transmural MI was induced in middle-aged, Sprague-Dawley rats by permanent ligation of the left anterior descending coronary artery. To recognize proliferating cells, rats were infused with 5-bromo-2'-deoxyuridine (BrdU) in a dose of 12.5 mg/kg/day for 72 hours via intraperitoneal osmotic minipumps on day 0, 4, or 11 after surgery. The rats were euthanized on day 3, 7 and 14 after MI, and their hearts were processed for histology and immunostaining. Results: Three days after MI, CD34+ SC/TCs were absent within the necrotic myocardial tissue but were visible around the surviving cardiac myocytes (CMs) bordering the infarcted region, including those remaining in subepicardial and subendocardial regions, and in the adventitia of residual coronary vessels. Seven days after MI, many of the CD34+ SC/TCs located at the periphery of the developing scar appeared enlarged and contained the BrdU labeling, indicating the cell proliferation. At the same time, elongated CD34+ SC/TCs, which lacked BrdU labeling, were noticed closer to the necrotic zone residing in the interstitial areas between the intact basement membranes left from resorbed CMs, suggesting their migratory activity. Fourteen days after MI, CD34+ SC/TCs were distributed throughout the entire post-infarcted region except for the areas occupied by necrotic tissue, myofibroblast-rich granulation tissue, and the fibroelastic thickenings of the endocardium affected by an MI. Furthermore, accumulated clusters of flattened CD34+ SC/TCs cells were apparent in the areas where the edges of surviving CMs extend into the fibrotic portion of the scar. Conclusion: These findings, for the first time, demonstrate that a population of myocardial CD34+ SC/TCs follow a dynamic pattern of spatiotemporal distribution within the healing myocardium suggesting their direct involvement in post-MI repair process and scar formation.