Intra-arterial bone marrow cell transplantation induces angiogenesis in rat hindlimb ischemia.

Abstract

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.

CONCLUSION:

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.

• Authors: M Yoshida, H Horimoto, S Mieno, Y Nomura, H Okawa, K Nakahara, S Sasaki
• Journal: European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes (Eur Surg Res) 2003 Mar-Apr Vol. 35 Issue 2 Pg. 86-91 ISSN: 0014-312X [Print] Switzerland
• PMID: 12679617 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2003 S. Karger AG, Basel

Chemical References

• Platelet Endothelial Cell Adhesion Molecule-1

Topics

• Angiography
• Animals
• Bone Marrow Transplantation
• Hindlimb (blood supply)
• Immunohistochemistry
• Infusions, Intra-Arterial
• Ischemia (physiopathology, therapy)
• Male
• Muscle, Skeletal (chemistry)
• Neovascularization, Physiologic (physiology)
• Platelet Endothelial Cell Adhesion Molecule-1 (analysis)
• Rats
• Rats, Inbred Lew
• Skin Temperature