Transplantation of bone marrow mesenchymal stem cells promotes recovery of renal ischemia-reperfusion injury in rats
Ting ZHANG; Yun ZHOU; Ya ZHANG; Zhi-hua HONG; Xiang-ming YAN
2008, 28(8):
825-830.
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Objective To investigate the therapy effects of bone marrow mesenchymal stem cells (MSCs) on renal recovery after ischemia-reperfusion injured. Methods 72 Spargue-Dawley rats(220-280g, 6 weeks old) were randomly assigned into 4 groups. (1)normal control(n=6), (2)sham operated control(n=6), (3)the I/R group( n=30), rats were subjected to 45 min bilateral renal ischemial-reperfusion injury with microvascular clips, after 60 min of reperfusion they were injected saline intravenously, (4)the MSCs group(n=30), rats were subjected to 45 min bilateral renal ischemial-reperfusion injury with microvascular clips, after 60 min of reperfusion they were injected in BrdU positive MSCs(1×106/ml)intravenously. The animals were sacrificed at 12h, 3d, 7d, 14d, and 42d after reperfusion, so the bilateral kidney and blood samples were harvested. The blood urea nitrogen(BUN) and serum creatinine(Scr) were measured on automatic biochemistry analyzer. Renal morphologic changes were scored with Paller's criterion on hematoxylin and eosin(H&E) stained sections. The apoptosis of tubular cells were examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). PCNA positive tubular cells were detected immunohistochemically as proliferation index. And confocal microscopy were used to identified the distribution of BrdU positive MSCs. Results After 12h, 3d of reperfusion, the Scr value of MSCs group were signifcantly lower than I/R group(P <0.05), the BUN value of MSCs group were lower than I/R group(P <0.05 ) . After 12h, 3d, and 7d of reperfusion the renal morphologic score of MSCs group were evidently lower than I/R group(P < 0.05). After 12h of reperfusion, the apoptosis tubular cells were much less than I/R group(P < 0.05). MSCs inhanced tubular proliferation at 12h, 3d, and 7d after reperfusion(P < 0.05). 42d after reperfusion, a few BrdU-positive cells were located at renal tubuli. Conclusions MSCs is of therapeutical value to renal ischemia-reperfusion injury, ameliorating the tissue damage,contributing to renal function recovery, and MSCs may also differentiate into renal tubular cells in vivo.