Autologous bone marrow implantation induced angiogenesis and improved deteriorated exercise capacity in a rat ischemic hindlimb model.
BACKGROUND
Bone marrow possesses endothelial progenitor cells that secrete several growth factors and can contribute to the formation of new capillaries. In the present study, we investigated the extent of angiogenesis induced by implantation of autologous bone marrow cells (BMCs) in a rat ischemic hindlimb model and studied whether the increased collateral vessels can improve deteriorated physical function.


METHODS
Ischemic hindlimb was created by ligation of the femoral artery and its branches in Dark Agouti (DA) rats. BMCs (1 x 10(7)) were injected percutaneously at six points into the gastrocnemius muscle. To assess angiogenesis, histologic evaluation and microangiography were performed at 2 weeks postligation. Severity of the ischemic insult was evaluated by measuring blood flow in the adductor and gastrocnemius muscles using nonradioactive colored microspheres and by determining the femoral arteriovenous oxygen difference (AVDO(2)) at 2 weeks postligation. Running time on a motor-driven treadmill was used to represent exercise capacity.


RESULTS
The histologic evaluation and microangiogram showed that the implanted BMCs induce angiogenesis. Blood flow to the adductor muscle on the treated side in the bone marrow cell implantation (BMI) group was significantly restored to 77.3 +/- 19.3% of that of the normally perfused limb in comparison to that in control groups (P < 0.05). AVDO(2) in the BMI group significantly decreased when compared with AVDO(2) in control groups. Rats in the BMI group ran approximately 1.5 times longer than rats in control groups at 2 and 4 weeks postligation (P < 0.01).


CONCLUSIONS
Implantation of autologous BMCs induced angiogenesis and improved deteriorated exercise capacity in our rat ischemic hindlimb model.
First Department of Surgery, First Department of Physiology, Second Department of Internal Medicine, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.
S
S
Ikenaga
K
K
Hamano
M
M
Nishida
T
T
Kobayashi
T S
TS
Li
S
S
Kobayashi
M
M
Matsuzaki
N
N
Zempo
K
K
Esato
D000792:Angiography; D000818:Animals; D016026:Bone Marrow Transplantation; D005552:Forelimb / Q000098:blood supply; D006614:Hindlimb / Q000098:blood supply* / Q000000981:diagnostic imaging; D007511:Ischemia / Q000503:physiopathology* / Q000601:surgery*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010101:Oxygen Consumption; D010807:Physical Endurance; D051381:Rats; D012039:Regional Blood Flow; D013997:Time Factors; D014182:Transplantation, Autologous