A dosing study of bone marrow mononuclear cells for transendocardial injection in a pig model of chronic ischemic heart disease.

We studied the effect of the dose of bone marrow mononuclear cells, delivered via transendocardial injection, upon capillary density and fibrosis in pigs with chronic ischemic heart disease. Pigs (n = 16) that had undergone ameroid constrictor placement (left circumflex coronary artery) to induce chronic ischemia were divided equally into 4 groups on the basis of bone marrow mononuclear cell dose: control (saline injection) and 50, 100, or 200 × 106 bone marrow mononuclear cells. Thirty days after ameroid placement, each pig received 13 transendocardial NOGA-guided injections. An implantable loop recorder monitored possible arrhythmias caused by cell transplantation. Thirty days later, the pigs were killed, and their hearts were evaluated histopathologically for fibrosis and capillary density; the number of cells per segment was correlated with fibrosis and capillary density. No adverse events, arrhythmias, or cardiac inflammatory reactions were associated with cell therapy. Less fibrosis was seen in pigs that received 100 × 106 cells than in control pigs. A trend toward higher capillary density was seen with higher cell concentrations. Segments injected with more than 20 × 106 million cells had the highest capillary density and the least amount of fibrosis (P < 0.05 vs controls). In conclusion, transendocardial injections (up to 200 × 106 bone marrow mononuclear cells) were safe. Analyses of individual injected segments suggest potential benefit from higher cell concentrations per segment.