Abstract 1858: Cardiac Engraftment and Distribution of Bone Marrow Stem Cells Implanted by Intravenous, Intracoronary and Intramyocardial Injections Using Molecular Imaging
Introduction: Following cell transplantation into the infarcted myocardium, conventional histology precludes longitudinal monitoring of implanted cell survival and engraftment. We used noninvasive bioluminescence imaging to visualize in living rats the distribution and engraftment of bone marrow stem cells (BMSCs) transfected with the firefly luciferase reporter gene (FL) and delivered by the 3 major routes for cardiac cell transplantation during the acute or chronic phase after myocardial infarction (MI).
Methods: FL was inserted into a replication-defective recombinant adenovirus and transfected into BMSCs cultured from male Lewis rats. MI was generated in female Lewis rats by left anterior descending artery ligation. Transfected BMSCs (3×106/rat) were implanted by intravenous (IV), introcoronary (IC), or intramyocarial (IM) injections at 3 or 28 days post-MI, or after sham procedures (control) (N=4–5/group). Implanted cell distribution was assessed 2, 24 and 48 hours later. Heart, lung, spleen, liver and kidney were explanted at 48 hours for cell quantification using RT-PCR.
Results: The systemic distribution of FL activity was diffuse following IC injection, but localized to the chest after IM or IV injections. IM injection yielded greater bioluminescence than IC or IV at all time points (P<0.05). Imaging of explanted organs at 48 hours revealed FL activity was localized predominantly in kidneys, lungs, and heart after IC injection, in heart and lungs after IM injection, and in lungs after IV injection. The cell distribution patterns determined by imaging were strongly correlated with those obtained by RT-PCR quantification of donor Y-chromosomes (r2>0.80 for all 3 cell delivery routes). More cells were retained in the infarcted myocardium when cells were delivered (IC or IM) at 28 days rather than 3 days after MI (P<0.05). Of the 3 routes, IM injection produced the most cardiac engraftment.
Conclusions: In living rats, molecular imaging effectively tracked the fate of BMSCs implanted by clinically adopted techniques, and agreed with the data obtained by RT-PCR. The results suggest that delivery of cells to the infarcted myocardium is most efficiently accomplished by IM injection during the chronic phase after MI.