Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: Implications for current clinical trials

• Published in: Circulation (New York, N.Y.) N.Y.), 2005-08, Vol.112 (9), p.I150-I156
• Main Authors: DONGMING HOU, YOUSSEF, Eyas Al-Shaykh, BRINTON, Todd J, PING ZHANG, ROGERS, Pamela, PRICE, Erik T, YEUNG, Alan C, JOHNSTONE, Brian H, YOCK, Paul G, MARCH, Keith L
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Cell Lineage; Cell Movement; Cell Survival; Cell Transplantation - methods; Clinical Trials as Topic - methods; Coronary heart disease; Coronary Vessels; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Fundamental and applied biological sciences. Psychology; Graft Survival; Heart; Humans; Infusions, Intravenous; Injections, Intramuscular; Kidney - pathology; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - transplantation; Liver - pathology; Lung - pathology; Male; Medical sciences; Myocardial Infarction - pathology; Myocardial Infarction - surgery; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - surgery; Myocardium - pathology; Organometallic Compounds - pharmacokinetics; Oxyquinoline - analogs & derivatives; Oxyquinoline - pharmacokinetics; Radiopharmaceuticals - pharmacokinetics; Random Allocation; Reproducibility of Results; Research Design; Spleen - pathology; Sus scrofa; Tissue Distribution; Transplantation, Heterologous; Vertebrates: cardiovascular system
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.104.526749

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. Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10(7) 111indium-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 gamma-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