Therapeutic angiogenesis induced by local autologous bone marrow cell implantation.
BACKGROUND
Therapeutic angiogenesis was induced by local autologous bone marrow cell implantation (BMCI) in ischemic hindlimb or ischemic heart models in rats. This study was designed to investigate the toxicity and therapeutic potency of local BMCI using a chronic coronary occlusion model in dogs.


METHODS
The canine chronic coronary occlusion model was created by ligating of the left anterior descending artery (LAD). The myocardium in the left ventricle was divided into distinct normal, marginal, and infarction areas 30 days after LAD ligation. Each area was injected at two locations, with either 2 x 10(7) bone marrow cells (n = 7, BMCI group) or 0.1 mL phosphate-buffered saline (PBS) only (n = 7, PBS group), respectively. Hemodynamics were evaluated by a single ultrasonic transducer and echocardiography before and 30 days after the treatment. Angiogenesis was evaluated by vessel count 30 days after the treatment. The toxicity of BMCI treatment was also evaluated in 8 normal dogs by following changes in electrocardiography (ECG), echocardiography, local histology, and systemic biochemistry indexes.


RESULTS
There was a significantly higher percentage of wall thickening in the marginal area in the BMCI group than in the PBS group 30 days after treatment (14.5 +/- 2.28 versus 8.1 +/- 3.00, p = 0.002). Significantly more microvessels were observed in the marginal area in the BMCI group than in the PBS group 30 days after treatment (127.7 +/- 20.1 versus 88.0 +/- 10.2/field, p = 0.0007). No systemic or local toxicity was found following BMCI treatment in the acute or chronic phases.


CONCLUSIONS
BMCI treatment improved local wall thickening dynamics, presumably due to the angiogenesis induced by the treatment. This indicates that it might be a safe and effective therapy for ischemic heart disease.
Hamano
Kimikazu
K
First Department of Surgery, Yamaguchi University School of Medicine, Ube, Japan. kimikazu@po.cc.yamaguchi-u.ac.jp
Li
Tao-Sheng
TS
Kobayashi
Toshiro
T
Hirata
Ken
K
Yano
Masafumi
M
Kohno
Michihiro
M
Matsuzaki
Masunori
M
D000818:Animals; D016026:Bone Marrow Transplantation; D017690:Cell Transplantation / Q000009:adverse effects; D003331:Coronary Vessels / Q000254:growth & development* / Q000473:pathology; D004285:Dogs; D004452:Echocardiography; D008833:Microcirculation / Q000473:pathology; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D014182:Transplantation, Autologous; D016277:Ventricular Function, Left