Effects of mesenchymal stem cells transplanted at different time points in a rat remnant kidney model.
OBJECTIVE
The optimal time for mesenchymal stem cell (MSCs) transplantation remains an unresolved issue. We compared the effects of MSCs on a rat remnant kidney model.


METHODS
Male Sprague-Dawley rats were randomly divided and treated with a corresponding reagent at 4, 8, 12 and 16 weeks, respectively. A remnant kidney model was established and MSCs were injected into rats. The migration of MSCs was then assessed by using cell-tracking experiments. Renal function and histological analyses were performed 4 weeks after MSC transplantation. Immunohistochemistry, Western blotting and real-time polymerase chain reaction were used to detect the TGF-β1 and α-SMA levels.


RESULTS
Four weeks after MSC injection, MSCs were found to migrate to the injured kidney. Significant histological damage improvement was observed after the treatment of MSCs at 4 and 8 weeks. The functional benefits of MSC treatment were observed in the 5/6 nephrectomy (Nx) + MSC group and the benefits were significantly higher at 4 and 8 weeks than at other time points (p < 0.05). Meanwhile, serum creatinine and urea levels as well as glomerular sclerosis and tubulointerstitial injury indexes were decreased at 4 and 8 weeks. Compared with the 5/6 Nx + PBS group, TGF-β1 and α-SMA levels were decreased in the 5/6 Nx + MSC group.


CONCLUSIONS
These data can be used to optimize the MSC transplantation time point as a therapeutic modality.
Department of Nephrology, The First Affiliated Hospital, China Medical University, Shenyang, China.
Xiaohui
X
Bian
Beiru
B
Zhang
Wei
W
Guo
Na
N
Liu
Yu
Y
Bai
Jianing
J
Miao
Guifeng
G
Zhao
Bo
B
Liu
Shubao
S
Wang
Li
L
Ma
Liqiang
L
Zheng
Yueyang
Y
Zhao
Detian
D
Li
Jiangmin
J
Feng
D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D003404:Creatinine / Q000097:blood; D005355:Fibrosis / Q000628:therapy; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood; D016030:Kidney Transplantation / Q000379:methods*; D007684:Kidney Tubules / Q000293:injuries; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014508:Urea / Q000097:blood
D000199:Actins; D003404:Creatinine; D016212:Transforming Growth Factor beta; D014508:Urea; C498862:Acta2 protein, rat