Quantitative assessment of initial retention of bone marrow mononuclear cells injected into the coronary arteries

• Published in: The Journal of heart and lung transplantation Vol. 30; no. 2; pp. 227 - 233
• Main Authors: Fukushima, Satsuki, MD, PhD, Campbell, Niall G., MRCP, Coppen, Steven R., PhD, Yamahara, Kenichi, MD, PhD, Yuen, Ada H.Y., BSc, Smolenski, Ryzard T., MD, PhD, Yacoub, Magdi H., FRS, Suzuki, Ken, MD, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.2011; Elsevier
• Subjects: Animals; Antigens, Ly - metabolism; Biological and medical sciences; Bone Marrow Cells - cytology; Bone Marrow Cells - physiology; Bone Marrow Transplantation - methods; bone marrow–derived stem cell; Cardiology. Vascular system; CD18 Antigens - metabolism; cell adhesion molecules; Cell Communication - physiology; cell transplantation; Coronary Vessels - pathology; Coronary Vessels - physiology; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; heart; Intercellular Adhesion Molecule-1 - metabolism; ischemia–reperfusion; Medical sciences; Membrane Glycoproteins - metabolism; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Animal; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - therapy; P-Selectin - metabolism; Regional Blood Flow - physiology; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Vascular Cell Adhesion Molecule-1 - metabolism; bone marrow–derived stem cell; cell transplantation; cell adhesion molecules; ischemia–reperfusion; heart; Mononuclear cell; Coronary artery; Bone marrow; Circulatory system; Cardiology; Retention; Phlebology; Quantitative analysis
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2010.09.002

Background Intracoronary injection of bone marrow mononuclear cells (BMMNC) is a common clinical protocol of cell transplantation for heart disease, but poor engraftment of donor cells in the heart, which will limit its therapeutic efficacy, is a major issue. Initial “retention” (endothelial adherence and/or extravasation) of BMMNC immediately after intracoronary injection is a key step toward successful engraftment; however, this event has not been fully characterized. The aim of this study is to quantitatively clarify the frequency of “retention” of BMMNC after intracoronary injection, determine the impact of prior induction of ischemia–reperfusion injury on “retention” efficiency, and elucidate the underlying mechanisms focusing on adhesion molecule–mediated cell–cell interactions. Methods One million BMMNC collected from green fluorescent protein (GFP)-transgenic mice were injected into the coronary arteries of syngeneic wild-type mouse hearts under Langendorff perfusion. Retention efficiency was quantitatively estimated from the GFP-positive cell number flushed out into the coronary effluent. Results Whereas only 13.3 ± 1.2% of injected BMMNC were retained into normal hearts, prior induction of 30-minute ischemia and 30-minute reperfusion increased the retention efficiency to 36.5 ± 1.6% ( p < 0.05, n = 8). Immunoconfocal observation further confirmed this enhanced retention after ischemia–reperfusion. Noticeably, the enhanced retention efficiency after ischemia–reperfusion treatment was diminished by administration of anti–P-selectin antibody (8.3 ± 0.8%, p < 0.05), but was not affected by inhibiting intercellular adhesion molecule-1 (39.6 ± 3.3%) or vascular cell adhesion molecule-1 (43.9 ± 2.9%). Conclusions Retention efficiency of intracoronary-injected BMMNC was poor in a model of isolated, crystalloid-perfused murine hearts. An antecedent period of global ischemia–reperfusion increased the retention via P-selectin–dependent BMMNC–endothelial interaction.