Published online before print March 15, 2007, doi: 10.1161/ATVBAHA.106.137141
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© 2007 American Heart Association, Inc.
Vascular Biology |
Synchrotron Radiation Coronary Microangiography for Morphometric and Physiological Evaluation of Myocardial Neovascularization Induced by Endothelial Progenitor Cell Transplantation
From Stem Cell Translational Research (H.I., A.K., A.O., S.H., T.M., M.I., H.N., Y.M., M.H., T.A.), Kobe Institute of Biomedical Research and Innovation/RIKEN Center for Developmental Biology; the Department of Cardiovascular Surgery (H.I., T.S., H.H., S.S.), Osaka City University Graduate School of Medicine; the Department of Image-based Medicine (K.F.), Kobe Institute of Biomedical Research and Innovation; the Department of Radiology (K.F., K.S.), Kobe University Graduate School of Medicine; the Research & Utilization Division (K.U.), Japan Synchrotron Radiation Research Institute, SPring-8, Sayo; and the Department of Regenerative Medicine Science (T.A.), Tokai University School of Medicine, Isehara, Japan.
Correspondence to Takayuki Asahara, MD, Stem Cell Translational Research, Kobe Institute of Biomedical Research and Innovation/RIKEN Center for Developmental Biology, 2-2 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. E-mail asa777{at}aol.com
Background— Therapeutic effect of stem cell transplantation (SCTx) for myocardial neovascularization has been evaluated by histological capillary density in small animals. However, it has been technically difficult to obtain imaging evidence of collateral formation by conventional angiography.
Methods and Results— Peripheral blood CD34+ and CD34– cells were isolated from patients with critical limb ischemia. PBS, CD34– cells, or CD34+ cells were intramyocardially transplanted after ligating LAD of nude rats. Coronary angiography of ex vivo beating hearts 5 and 28 days after the treatment was performed using the third generation synchrotron radiation microangiography (SRM), which has potential to visualize vessels as small as 20 µm in diameter. The SRM was performed pre and post sodium nitroprusside (SNP) to examine vascular physiology at each time point. Diameter of most collateral vessels was 20 to 120 µm, apparently invisible size in conventional angiography. Rentrop scores at day 28 pre and post SNP were significantly greater in CD34+ cell group than other groups (P<0.01). To quantify the extent of collateral formation, angiographic microvessel density (AMVD) in the occluded LAD area was analyzed. AMVD on day 28 post SNP, not pre SNP, was significantly augmented in CD34+ cell group than other groups (P<0.05). AMVD post SNP closely correlated with histological capillary density (R=0.82, P<0.0001).
Conclusions— The SRM, capable of visualizing microvessels, may be useful for morphometric and physiological evaluation of coronary collateral formation by SCTx. The novel imaging system may be an essential tool in future preclinical/translational research of stem cell biology.
Therapeutic effect of stem cell transplantation (SCTx) for myocardial neovascularization has been evaluated by histological capillary density in small animals. However, it has been technically difficult to obtain imaging evidence of collateral formation by conventional angiography. The present results indicate that the synchrotron radiation microangiography (SRM) may be useful to both morphologically and physiologically evaluate therapeutic neovascularization by SCTx in small animals. The novel imaging system may be an essential tool in future preclinical/translational research of stem cell biology. Further development of in vivo imaging system in future may lead to clinical application of the SRM.
Key Words: synchrotron radiation microangiography • image • CD34+ cells • neovascularization • myocardial infarction