Abstract 3125: Noninvasive Imaging of Bone Marrow Stem Cell Homing, Survival, and Proliferation in Ischemic Myocardium
Background: Bone marrow mononuclear cell (BMMC) therapy shows promise for treatment of ischemic heart disease. However, the ability to monitor delivered cell fate remains limited.
Hypothesis: Reporter gene imaging can be used to track stem cell homing after myocardial ischemia-reperfusion (I/R) injury. Methods: Adult female FVB recipient mice were randomized to 30-min of LAD artery I/R (n=15) or sham surgery with thoracotomy but no I/R (n=15). Afterwards, animals received 5×106 BMMCs via tail vein injection. BMMCs were harvested from adult male L2G transgenic donors constitutively expressing GFP and firefly luciferase (Fluc) reporter genes. Cell homing was monitored by bioluminescence imaging (BLI) for 4 weeks using D-Luciferin (375 mg/kg, ip) as the reporter probe.
Results: BMMC number correlated robustly with Fluc activity (r2=0.95) and FACS analysis demonstrated ~0.07% of the total population to be hematopoietic stem cells (lin-, sca-1+, c-kit+). For up to one week following injection, BLI signals were significantly higher in the I/R group compared to sham (P<0.05, Figure 1⇓). Imaging results were validated by postmortem Fluc enzyme assay and histology. Quantitative RT-PCR probing for male donor cells (SRY gene) in the female recipients also confirmed higher number of BMMCs in I/R hearts (4293±2212) vs. sham (1882±1402) at week 2 (P<0.05).
Conclusions: Reporter gene imaging successfully demonstrates BMMCs preferentially home to injured myocardium. Current studies are focusing on understanding the paracrine factors mediating homing. With further validation, molecular imaging analysis can provide significant insights into stem cell biology and physiology in vivo.