Human unrestricted somatic stem cell administration fails to protect nude mice from cisplatin-induced acute kidney injury.
BACKGROUND
Kidney failure is a debilitating disorder with limited treatment options. The kidney-protective effects of stem cells have been vastly investigated and promising results have been achieved with various sources of stem cells. However, in spite of beneficial effects on other disease models, the renoprotective potential of human cord blood-derived unrestricted somatic stem cells (USSC) has not been examined so far.


METHODS
In the present study, acute kidney failure was induced in female nude mice and the effect of USSC transplantation on kidney function and structure was assessed. Furthermore, the expression of some cytokine genes was examined by real-time PCR. Homing of the transplanted cells into kidneys was assessed by flow cytometry, immunohistochemistry, and real-time PCR.


RESULTS
USSC-conditioned medium did not attenuate the in vitro nephrotoxic effects of cisplatin. Transplantation of USSC to nude mice did not protect kidney function and was associated with worsened kidney structural damage. USSC transplantation was also associated with a decline in the renal expression of VEGF-A gene. In spite of these effects, the transplanted cells could not be detected in the kidneys by any of the exploited methods and they were mainly entrapped in the lungs.


CONCLUSIONS
These data indicate that USSC are not suitable for cell therapy in the setting of acute kidney injury. Also, this study shows that these stem cells are able to affect damaged kidneys even if they are not homed there.
Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran.
Yousof
Y
Gheisari
Naser
N
Ahmadbeigi
Seyed Hamid
SH
Aghaee-Bakhtiari
Seyed Mahdi
SM
Nassiri
Saeid
S
Amanpour
Kayhan
K
Azadmanesh
Athena
A
Hajarizadeh
Zahra
Z
Mobarra
Masoud
M
Soleimani
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000235:genetics / Q000601:surgery*; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D015703:Antigens, CD; D017077:Culture Media, Conditioned; D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; D002945:Cisplatin