Exogenous Hematopoietic Stem Cells Can Regenerate Infarcted Myocardium
To determine whether hematopoietic stem cells (HSC) can transform into cardiomyocytes with the potential to repair dead myocardium after infarction, Lin/c-kitI-II HSC were harvested from transgenic mice expressing green fluorescent protein (GFP) and injected in the region bordering the infarct, 3–5 hours after coronary artery occlusion in mice. A band of closely packed cells was identified 7 to 17 days later in nearly 50% of HSC injected hearts, between the endocardial and epicardial surface of the infarcted ventricle. This band occupied 50 75% of the damaged portion of the wall. c-kit/GFP positive HSC were found in the infarcted area shortly after coronary ligation and were still detectable at 7 days. c-kit stained HSC were not labeled by markers of myocytes, α-sarcomeric actin and myosin, endothelial cells, factor VIII, and smooth muscle cells, smooth muscle actin. The band of tissue included in the infarcted zone was constituted 75% by GFP, α-sarcomeric actin, myosin and α-actinin positive cardiac muscle cells. Other GFP-positive cell populations were endothelial cells and smooth muscle cells, organized in nascent capillary structures and arterioles. Proliferating myocytes were small with partially aligned myofibrils and resembled late fetal-neonatal cells. GFP-positive replicating myocytes, endothelial cells and smooth muscle cells were c-kit negative. Infarcted mice were injected with BrdU, once a day for 4 days, to establish the extent of cell proliferation in the regenerating myocardium: 28% myocytes, 17% endothelial cells and 12% smooth muscle cells were BrdU positive. These three levels of BrdU labeling were statistically different. Additionally, the percentages of cells positive to Ki67 were measured to evaluate the fraction of cycling cells at this stage of repair: 18% myocytes, 10% endothelial cells and 8% smooth muscle cells were in G1-G2M. In conclusion, HSC, when injected in the heart, rapidly differentiate into myocardium resulting in significant recovery of muscle mass after infarction.
- Copyright © 2000 by American Heart Association