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Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1804-1810
Published online before print September 26, 2002, doi: 10.1161/01.ATV.0000039168.95670.B9
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1804.)
© 2002 American Heart Association, Inc.


Vascular Biology

Improvement of Collateral Perfusion and Regional Function by Implantation of Peripheral Blood Mononuclear Cells Into Ischemic Hibernating Myocardium

Hiroshi Kamihata*; Hiroaki Matsubara; Takashi Nishiue*; Soichiro Fujiyama*; Katsuya Amano*; Osamu Iba; Takanobu Imada; Toshiji Iwasaka

From the Department of Medicine II and Cardiovascular Center, Kansai Medical University, Moriguchi, Osaka, Japan.

Correspondence to Hiroaki Matsubara, MD, Department of Medicine II, Kansai Medical University, Moriguchi, Osaka 570-8507, Japan. E-mail matsubah{at}takii.kmu.ac.jp

Objective— This study was performed to evaluate the angiogenic effect of implantation of peripheral blood mononuclear cells (PB-MNCs) compared with bone marrow mononuclear cells (BM-MNCs) into ischemic hibernating myocardium.

Methods and Results— A NOGA electromechanical system was used to map the hibernating region and to inject cells. PB-MNCs and BM-MNCs contained similar levels of vascular endothelial growth factor and basic fibroblast growth factor, whereas contents of angiogenic cytokines (interleukin-1ß and tumor necrosis factor-{alpha}) were larger in PB-MNCs. Numbers of endothelial progenitors were {approx}500-fold higher in BM-MNCs. In BM-MNC–implanted myocardia of pigs, an increase in systolic function (ejection fraction from 33% to 52%) and regional blood flow (2.1-fold) and a reduction of the ischemic area (from 29% to 8%) were observed. PB-MNC implantation reduced the ischemic area (from 31% to 17%), the extent of which was less than that seen with BM-MNCs. In saline-implanted myocardium, the ischemic area expanded (from 28% to 38%), and systolic function deteriorated. Angiography revealed an increase in collateral vessel formation by PB-MNC or BM-MNC implantation. Capillary numbers were increased 2.6- and 1.7-fold by BM-MNC and PB-MNC implantation, respectively. BM-MNCs but not PB-MNCs were incorporated into neocapillaries.

Conclusions— Catheter-based implantation of PB-MNCs can effectively improve collateral perfusion and regional function in hibernating ischemic myocardium by its ability to mainly supply angiogenic factors and cytokines.


Key Words: angiogenesis • myogenesis • bone marrow • stem cells • ischemic myocardium




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