Ultrasound Irradiation-Mediated Microbubble Destruction Enables Highly Efficient Local Delivery of Bone Marrow Cells Into Chronic Ischemic Myocardium and angiogenesis.

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13670759
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kansai Medical University
• Principal Investigator: NISHIUE Takashi Kansai Medical University, Faculty of Medicine, Instructor, 医学部, 助手 (30319628)
• Project Period (FY): 2001 – 2002
• Keywords: microbubble / ultrasound / angiogenesis / ischemic heart disease / bone marrow cell

Research Abstract

We have developed a novel technique, which efficiently delivers bone marrow-mononuclear cells (BM-MNCs) into ischemic myocardium by ultrasound-mediated microbubble destruction. Methods: Chronic ischemic cardiomyopathy was produced by placing Ameroid constrictor on both LAD and LCX in dogs. One month after the operation, microbubble-contrast agent (Optison) was infused into the left coronary artery (LCA) followed by ultrasound irradiation(US) (1MHz, 2W/cm^2, 1 minute) to the heart. Immediately after US, labeled BM-MNCs(2× 10^8 cells) were infused into LCA(n=5). As a negative control, only US to the heart with Optison, was performed(n=5). As a positive control, only BM-MNCs were infused into LCA (n=5). Results: Four weeks after treatment, intracoronary infusion coupled with Optison-US showed marked incorporation of BM-MNCs into 70-80% of neocapillaries, whereas transplantation without Optison-US resulted in much lower incorporation ratio(〜5%). BM-MNCs were also detected in arterioles >50μm, while differentiation into cardiomyocyte was very few. Regional myocardial blood flow evaluated by color microspheres increased 2.5 fold 1 month after BM-MNCs with Opsison-US treatment but not in positive and negative control groups. These findings corresponded to an increase in ejection fraction (38.2±0.9 to 63.0±5.0%) at rest and %wall thickening (13.6±5.2 to 50.7±17.8%) during dubutamine stress. Conclusion: This novel technique permits efficient cell delivery into ischemic heart. US-induced local BM-MNCs delivery has an excellent potential for therapeutic angiogenesis and cardiomyogenesis.