Abstract 14661: Tadalafil Mobilizes Progenitor Cells From Bone Marrow and Promotes Homing Into Ischemic Myocardium
Background: Tadalafil promotes mobilization of progenitor cells and improves endothelial function in patients with erectile dysfunction. The role of tadalafil and homing of stem cells in ischemic heart disease is poorly understood. To unravel the homing effect of tadalafil-mediated stem cell trafficking after myocardial infarction (MI) was investigated.
Methods and results: Female mice underwent LAD ligation then IP injections of tadalafil (20 mg/kg) followed by IV injection of male donor MSCs expressing green fluorescent protein (GFP, 2х106) labeled with 37 MBq 111In-oxine (half-life: 2.8d) via the tail. After labeling, cell viability was assessed using trypan-blue. Combined SPECT/CT imaging was performed at 2h, 24h, and 48h. Histopathology and bio-distribution of selected organs was performed at 7 days post MI. Mean cell labeling efficiency of 111In-oxine was 95.2% and cell viability after labeling averaged 90%. A transient high lung uptake was observed within the first 2h after infusion of MSCs in both groups. At 24h after injection, the initial lung activity shifted toward liver, kidneys, spleen, and heart in the tadalafil vs the controls. At day 7, the specific activity (MBq/g tissue) of heart increased in tadalafil (0.003 ± 0.001) vs control (0.001±0.001) (P=0.003) in infarcted hearts. However, the overall specific radioactivity detected in the heart was 17.5% (tadalafil) vs 3.6% (control). The specific activity found in the remaining organs for tadalafil vs control was: lung (0.006 ± 0.001 vs 0.016 ± 0.009, P=0.04), kidney (0.034 ± 0.018 vs 0.027 ± 0.02, P=0.65), liver (0.016 ± 0.01 vs 0.019 ± 0.007, P=0.64), and spleen (0.012 ± 0.009 vs 0.016 ± 0.002, P=0.51). Ex-vivo fluorescent imaging revealed significant uptake of GFP-MSCs in the tadalafil vs the control hearts. Tadalafil induced a significant increase in progenitor cells (Sca1+, c-kit+, CD31+ and CD34+) in the infarcted heart compared to controls.
Conclusions: Cell labeling with 111In-oxine is a suitable non-invasive method for tracking MSC distribution, sequential monitoring of therapeutic stem cells, and assessing the homing effect of drugs. Tadalafil induces bone marrow progenitor cell mobilization and enhances MSC homing needed in the recovery of ischemic myocardium.
- © 2013 by American Heart Association, Inc.