Background— Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model. Methods and Results— Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10 7 111 indium-oxine–labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by γ-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26±3% (IM), 47±1% (IC), and 43±3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11±3%) compared with IC (2.6±0.3%) ( P <0.05) delivery. IRV delivery efficiency (3.2±1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques. Conclusions— The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.

Myocardial delivery of genes holds great promise for treating many heart diseases; however, the optimal delivery technique, which maximizes safety and efficacy, has not been established. Two delivery techniques were evaluated in swine; percutaneous retrograde coronary venous delivery (RCVD) and direct intramyocardial injection (IM). RCVD was performed in the anterior interventricular vein (AIV) with an end-hole occlusion balloon catheter. The plasmid gWiz, encoding beta-galactosidase (10 ml; 1 mg/ml), was injected using either manual high pressure (HP-RCVD; n = 5) or pressure wire-guided low pressure (LP-RCVD; n = 4). For the IM group (n = 4), beta-Gal plasmid (5 mg/ml) was injected at 10 sites (200 microl/site) in the anterior left ventricular wall. Animals were euthanized after 5 days. The percentage of beta-Gal expressing cells in the delivered region was higher in the HP-RCVD (0.26% +/- 0.05%) than the LP-RCVD (0.05% +/- 0.03%; P = 0.07) and IM groups (0.02% +/- 0.01%; P = 0.01). Myocardium from the HP-RCVD group contained 7- and 17-fold higher levels of beta-Gal activity than either LP-RCVD and IM groups, respectively (P = 0.05 for both). The results of this study confirm the safety and efficacy of RCVD for myocardial gene delivery.

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