Adipose-derived stem cell transplantation for acute kidney injury caused by crush injury / 中国组织工程研究

ABSTRACT

BACKGROUND: Adipose-derived stem cells have the advantages of easy access, easy separation, small trauma, and rapid proliferation. Current treatments for kidney injury are more limited, and adipose-derived stem cells may provide a new treatment route. OBJECTIVE: To investigate the effects of adipose-derived stem cell transplantation on the kidney function of rats with acute kidney injury induced by crush injury in rats. METHODS: Cryopreserved adipose-derived stem cells were recovered in vitro and cultured to prepare cell suspension following labeling with PKH-26. Twenty rats were randomly selected from 66 experimental Sprague-Dawley rats (provided by Beijing Vital River Laboratory Animal Technology Co., Ltd.) as normal control group. In the 40 of the remaining 46 rats, a pathological model of acute kidney injury caused by compression injury was successfully established by the use of forceps to double the proximal hind limbs. The 40 rat models were divided into model group and cell transplantation group, with 20 rats in each group. After 6 hours of modeling, the rats in the model group were given intravenous injection of normal saline (20 μL) , and the rats in the cell group were given intravenous injection of PKH-26-labeled adipose-derived stem cells (20 μL, 3×106/L) , once a day for 3 continuous days. The levels of serum creatinine and urea nitrogen were measured in each group at 1, 3, 14 and 21 days after transplantation. The left kidney of the rats in each group was observed using hematoxylin-eosin staining, TUNEL staining, RT-PCR and western blot assay at 3 and 21 days after cell transplantation. RESULTS AND CONCLUSION: (1) The levels of creatinine and urea nitrogen in the serum of rats at 1, 3, 14 and 21 days after cell transplantation were significantly higher in the model group than the normal control group (P < 0.05) and cell transplantation group (P < 0.05). (2) At 3 and 21 days after cell transplantation, the scores on the kidney injury and apoptotic rate of kidney cells were ranked as follows: model group> cell transplantation group> normal control group, and there were significant differences between groups (P < 0.05). (3) At 3 and 21 days after cell transplantation, the expressions of bax and Caspase-3 in the kidney tissue at mRNA and protein levels were significantly higher in the model group and cell transplantation than the normal control group (P < 0.01) as well as significantly higher in the cell transplantation group than the model group (P < 0.05). To conclude, adipose-derived stem cell transplantation has obvious repairing effect on acute kidney injury caused by crush injury, and its mechanism may be related to the involvement of adipose-derived stem cells in regulating the expression of bax and Caspase-3.