Novel autologous cell therapy in ischemic limb disease through growth factor secretion by cultured adipose tissue-derived stromal cells.
OBJECTIVE
The delivery of autologous progenitor cells into ischemic tissue of patients is emerging as a novel therapeutic option. Here, we report the potential impact of cultured adipose tissue-derived cells (ADSC) on angiogenic cell therapy.


RESULTS
ADSC were isolated from C57Bl/6 mouse inguinal adipose tissue and showed high expression of ScaI and CD44, but not c-kit, Lin, CD34, CD45, CD11b, and CD31, compatible with that of mesenchymal stem cells from bone marrow. In coculture conditions with ADSC and human aortic endothelial cells (ECs) under treatment with growth factors, ADSC significantly increased EC viability, migration and tube formation mainly through secretion of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). At 4 weeks after transplantation of ADSC into the ischemic mouse hindlimb, the angiogenic scores were improved in the ADSC-treated group, which were evaluated with blood flow by laser Doppler imaging (LDI) and capillary density by immunostaining with anti-CD31 antibody. However, injected ADSC did not correspond to CD31, von Willebrand factor, and alpha-smooth muscle actin-positive cells in ischemic tissue.


CONCLUSIONS
These adipose tissue-derived cells demonstrated potential as angiogenic cell therapy for ischemic disease, which appears to be mainly achieved by their ability to secrete angiogenic growth factors.
Nakagami
Hironori
H
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan. nakagami@gts.med.osaka-u.ac.jp
Maeda
Kazuhisa
K
Morishita
Ryuichi
R
Iguchi
Sota
S
Nishikawa
Tomoyuki
T
Takami
Yoichi
Y
Kikuchi
Yasushi
Y
Saito
Yukihiro
Y
Tamai
Katsuto
K
Ogihara
Toshio
T
Kaneda
Yasufumi
Y
D000273:Adipose Tissue / Q000166:cytology*; D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology; D002455:Cell Division; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology; D006133:Growth Substances / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D018919:Neovascularization, Physiologic / Q000502:physiology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042683:Angiopoietin-1; D016207:Cytokines; D006133:Growth Substances; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D017228:Hepatocyte Growth Factor