Autologous cell therapy for cisplatin-induced acute kidney injury by using non-expanded adipose tissue-derived cells.
OBJECTIVE
Recent studies have demonstrated that cultured mesenchymal stromal cells derived from adipose tissue are useful for regenerative cell therapy. The stromal vascular fraction (SVF) can be obtained readily without culturing and may be clinically applicable. We investigated the therapeutic effects of SVF and used it in the treatment of acute kidney injury (AKI).


METHODS
Liposuction aspirates were obtained from healthy donors who had provided written informed consent. We harvested the SVF and determined the growth factor secretion and anti-apoptotic ability with conditioned medium. To investigate the effect of SVF on AKI, cisplatin was injected into rats and SVF was administrated into the subcupsula of the kidney.


RESULTS
Both human and rat SVF cells secreted vascular endothelial growth factor-A (VEGF) and hepatocyte growth factor (HGF). Human SVF-conditioned media had an anti-apoptotic effect, which was inhibited by anti-HGF antibody (Ab) but not by anti-VEGF Ab. In vivo, SVF significantly ameliorated renal function, attenuated tubular damage and increased the cortical blood flow speed. In the SVF-treated group, VEGF levels in the cortex and HGF levels in both the cortex and medulla, especially tubules in the medulla, were significantly higher. Immunostaining revealed that SVF cells expressing VEGF and HGF and remained in the subcapsule on day 14.


CONCLUSIONS
The present study demonstrates that a subcapsular injection of non-expanded SVF cells ameliorates rat AKI, and that the mechanism probably involves secretion of renoprotective molecules. Administration of human SVF may be clinically applicable and useful as a novel autologous cell therapy against kidney diseases.
Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan. kyasuda@med.nagoya-u.ac.jp
Kaoru
K
Yasuda
Takenori
T
Ozaki
Yousuke
Y
Saka
Tokunori
T
Yamamoto
Momokazu
M
Gotoh
Yasuhiko
Y
Ito
Yukio
Y
Yuzawa
Seiichi
S
Matsuo
Shoichi
S
Maruyama
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000628:therapy*; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D002945:Cisplatin / Q000008:administration & dosage; D017077:Culture Media, Conditioned / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000648:ultrastructure; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D014182:Transplantation, Autologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D002945:Cisplatin