Neovasculature in bone marrow stem cell mobilization for treating myocardial infarction

Stem cell therapy offers a potential venue with which autologous bone marrow-derived stem cells (BMDSC) have the potential to regenerate functioning myocardial tissue in situ soon after myocardial infarction (MI). When they migrate to sites of MI, they can differentiate into cardiomyocytes, endothelial cells and nerve cells. We have developed a method to substantially increase the small amounts of circulating BMDSC following MI. Rebuilt myocardium must include a vascular network able to nourish it under diverse metabolic demands. We intend to quantify the viability and functionality of the microvasculature 1-4 weeks post MI with or without BMDSC mobilization to assess the ability of this neovasculature to deliver oxygen to the tissue. Fluorescent staining is used to visualize perfused and nonperfused neovasculature, and immunohistochemical staining is used for quantification of tissue hypoxia. Our preliminary results indicate that the decrease in the number of anatomical and perfused vessels after MI, is accompanied by a progressive increase in the distance to the nearest perfused blood vessel and the level of hypoxia in the infarcted tissue. These preclinical studies may aid in design of BMDSC mobilization strategies to treat humans with MI.