Synchrotron radiation coronary microangiography for morphometric and physiological evaluation of myocardial neovascularization induced by endothelial progenitor cell transplantation.
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.


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 microm 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 microm, 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.
Iwasaki
Hiroto
H
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.
Fukushima
Kazuhito
K
Kawamoto
Atsuhiko
A
Umetani
Keiji
K
Oyamada
Akira
A
Hayashi
Saeko
S
Matsumoto
Tomoyuki
T
Ishikawa
Masakazu
M
Shibata
Toshihiko
T
Nishimura
Hiromi
H
Hirai
Hidekazu
H
Mifune
Yutaka
Y
Horii
Miki
M
Sugimura
Kazuro
K
Suehiro
Shigefumi
S
Asahara
Takayuki
T
D000368:Aged; D000818:Animals; D006348:Cardiac Surgical Procedures; D003097:Collateral Circulation; D017023:Coronary Angiography / Q000379:methods*; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000473:pathology* / Q000503:physiopathology; D016638:Critical Illness; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D005121:Extremities / Q000098:blood supply; D005260:Female; D006801:Humans; D007511:Ischemia / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000000981:diagnostic imaging / Q000503:physiopathology; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000601:surgery; D009204:Myocardial Revascularization / Q000379:methods*; D018919:Neovascularization, Physiologic; D036102:Peripheral Blood Stem Cell Transplantation; D051381:Rats; D011923:Rats, Nude; D013234:Stem Cells / Q000473:pathology; D017356:Synchrotrons; D013997:Time Factors; D014183:Transplantation, Heterologous