Changes in angiogenesis-related factors in serum following autologous bone marrow cell implantation for severe limb ischemia.
OBJECTIVE
Bone marrow mononuclear cell (BM-MNC) implantation (BMI) for critical severe limb ischemia especially for Buerger's disease shows excellent clinical results but the mechanism of this treatment is still unknown. In this study, we investigated the changes in serum levels of angiogenesis-related factors after BMI treatment.


METHODS
Twelve patients whose BMI treatments were clinically very effective was selected out of ninteen cases, nine patients had Buerger's disease, two patients had arteriosclerosis obliterans and one had systemic sclerosis. Venous bood from femoral vein or brachial vein of the recipient limbs of these patients.


RESULTS
Adrenomedulin (AM), soluble vascular cell adhesion molecule-1 (sVCAM-1), and C-reactive protein (CRP) serum levels 24 h after BMI treatment were significantly increased compared with those before BMI treatment (p < 0.05). Vascular endothelial growth factor (VEGF) serum levels after BMI treatment significantly increased between 1 week and 3 months after BMI treatment (p < 0.05). Nitric oxide (NO) serum levels after BMI treatment increased significantly 2 weeks after BMI treatment (p < 0.05). There was no correlation between the numbers of implanted cells and serum levels of measured angiogenesis-related factors that were significantly increased after BMI treatment.


CONCLUSIONS
It was concluded that the mechanism underlying BMI treatment consists of early and late phases. The early phase involves the direct action by implanted cells, and the late phase involves indirect paracrine action. In addition, it was considered that BMI treatment is effective when we implant a sufficient level of bone marrow (600 ml) to treat severe limb ischemia.
Tachi
Yoshihito
Y
Shinshu University Graduate School of Medicine, Division of Cardiovascular Surgery, 3-1-1 Asahi Matsumoto Nagano, 390-8621, Japan.
Fukui
Daisuke
D
Wada
Yuko
Y
Koshikawa
Megumi
M
Shimodaira
Shigetaka
S
Ikeda
Uichi
U
Amano
Jun
J
D053607:Adrenomedullin / Q000097:blood; D000328:Adult; D000368:Aged; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000150:complications / Q000601:surgery; D002097:C-Reactive Protein / Q000032:analysis; D003289:Convalescence; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D018380:Hematopoietic Stem Cell Transplantation; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D053583:Interleukin-1beta / Q000097:blood; D007511:Ischemia / Q000097:blood* / Q000209:etiology / Q000601:surgery; D007866:Leg / Q000098:blood supply* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000150:complications / Q000601:surgery; D011184:Postoperative Period; D014182:Transplantation, Autologous; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
C507862:ADM protein, human; C066855:HGF protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; C467484:VEGFA protein, human; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D016179:Granulocyte Colony-Stimulating Factor; D053607:Adrenomedullin; D009569:Nitric Oxide; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D002097:C-Reactive Protein