Abstract 13072: Bone Marrow Reconstitution Restores Cardiac-Resident Stem Cells and Enhances Cardiac Repair after Infarction
Introduction: The adult heart retains a small population of progenitor cells that are essential for cardiac regeneration after injury. In aged individuals, these cells are diminished and dysfunctional, which may contribute to progressive heart failure. The derivation of these cardiac progenitors is debated, and methods to restore their number and function are required. We assessed the hypothesis that bone marrow (BM) rejuvenation can restore cardiac progenitor cells, which augment myocardial repair after injury.
Methods: Old female mice (22 months) were lethally irradiated and infused with 5×106 fresh BM cells from either young (2 months) or old male GFP mice to produce two groups of chimeras (n=60/group). Following an 8-week recovery, chimeric mice were again subjected to lethal irradiation followed by infusion of BM cells, but this time from old female donors. Some mice received whole-body irradiation (n=25); however, in some mice, the heart was protected from irradiation with a carefully positioned lead shield to create cardiac microchimerism (n=24). Myocardial infarction was induced by coronary artery ligation 3 days later. Real-time PCR determined the number of Y chromosomes in the aged female recipient hearts. Donor-derived progenitor cells in the heart were also quantified with flow cytometry and a colony-forming unit assay. Cardiac function was measured with echocardiography.
Results: Aged mice had fewer progenitors in both the BM (p<0.01) and myocardium (p<0.05). The diminished number correlated with the extent of ventricular dysfunction after injury (p<0.05). In aged mice, both the number of myocardial progenitors (p<0.05) and cardiac function (p<0.05) were restored when the BM was reconstituted with young, but not aged, BM cells. When cardiac microchimerism was established, ventricular function was restored when the cardiac nascent progenitor cells were derived from young BM prior to injury. The cardiac-resident progenitors in the aged myocardium actively proliferated (p<0.01) after myocardial injury and enhanced cardiac repair through paracrine mechanisms.
Conclusions: In aged individuals, BM reconstitution with young BM cells restored progenitors in both the BM and heart. The aged heart was rejuvenated with young BM cells.
- © 2011 by American Heart Association, Inc.