Intra-arterial bone marrow cell transplantation induces angiogenesis in rat hindlimb ischemia.
BACKGROUND
Bone marrow (BM) cells have been shown to augment local angiogenesis by differentiating vessels themselves and/or secreting paracrinally angiogenic growth factors. Herein, the angiogenic effects of intra-arterial BM mononuclear cell (BM-MNC) transplantation were evaluated in a rat ischemic hindlimb model.


METHODS
Unilateral hindlimb ischemia was created by excising the femoral artery and its branch in Lewis rats. BM-MNCs were isolated by centrifugation through a Histopaque density gradient. One week after excision of the unilateral femoral artery, BM-MNCs (5 x 10(6) cells, Group A, n = 6) or PBS (Group B, n = 7) were injected into the ischemic thigh skeletal muscles at the six points with a gauge needle. Another injection of BM-MNCs (3 x 10(7) cells, Group C, n = 6) or PBS (Group D, n = 7) was administered via the indwelling catheter in the right common iliac artery.


RESULTS
Four weeks after the BM-MNC transplantation, angiographic examination revealed the development of collateral vessels in both BM-MNC-transplanted groups. The difference in skin temperature between right and left hindlimbs was significantly reduced in both BM-MNC-transplanted groups (0.93 +/- 0.15 vs. 2.84 +/- 0.35 vs. 1.20 +/- 0.26 vs. 2.61 +/- 0.37 degrees C, Group A vs. Group B vs. Group C vs. Group D, p < 0.05). Moreover, immunohistochemical analysis demonstrated that capillary endothelial cells were increased in both BM-MNC-transplanted groups.


CONCLUSIONS
BM-MNC implantation was able to induce functional neovascularization in rat ischemic hindlimb. The intra-arterial administration offered similar levels of angiogenic activity as intramuscular injection.
Yoshida
M
M
Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, Takatsuki, Japan.
Horimoto
H
H
Mieno
S
S
Nomura
Y
Y
Okawa
H
H
Nakahara
K
K
Sasaki
S
S
D000792:Angiography; D000818:Animals; D016026:Bone Marrow Transplantation; D006614:Hindlimb / Q000098:blood supply; D007150:Immunohistochemistry; D007261:Infusions, Intra-Arterial; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D012881:Skin Temperature
D019408:Platelet Endothelial Cell Adhesion Molecule-1