Implantation of adipose-derived regenerative cells enhances ischemia-induced angiogenesis.
OBJECTIVE
Therapeutic angiogenesis using autologous stem/progenitor cells represents a novel strategy for severe ischemic diseases. Recent reports indicated that adipose tissues could supply adipose-derived regenerative cells (ADRCs). Accordingly, we examined whether implantation of ADRCs would augment ischemia-induced angiogenesis.


RESULTS
Adipose tissue was obtained from C57BL/6J mice, and ADRCs were isolated using standard methods. ADRCs expressed stromal cell-derived factor 1 (SDF-1) mRNA and proteins. Hind limb ischemia was induced and culture-expanded ADRCs, PBS, or mature adipocytes (MAs) as control cells were injected into the ischemic muscles. At 3 weeks, the ADRC group had a greater laser Doppler blood perfusion index and a higher capillary density compared to the controls. Implantation of ADRCs increased circulating endothelial progenitor cells (EPCs). SDF-1 mRNA abundance at ischemic tissues and serum SDF-1 levels were greater in the ADRC group than in the control group. Finally, intraperitoneal injection of an anti-SDF-1 neutralizing antibody reduced the number of circulating EPCs and therapeutic efficacies of ADRCs.


CONCLUSIONS
Adipose tissue would be a valuable source for cell-based therapeutic angiogenesis. Moreover, chemokine SDF-1 may play a pivotal role in the ADRCs-mediated angiogenesis at least in part by facilitating mobilization of EPCs.
Kondo
Kazuhisa
K
Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-8550 Japan.
Shintani
Satoshi
S
Shibata
Rei
R
Murakami
Hisashi
H
Murakami
Ryuichiro
R
Imaizumi
Masayasu
M
Kitagawa
Yasuo
Y
Murohara
Toyoaki
T
D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D000273:Adipose Tissue / Q000502:physiology / Q000637:transplantation*; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D054377:Chemokine CXCL12 / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D017930:Genes, Reporter; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000150:complications / Q000503:physiopathology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A