[Differentiation of mesenchymal stem cells into vascular endothelial cells in treatment of chronic aristolochic acid nephropathy: experiment with rats].
OBJECTIVE
To investigate the potentiality of mesenchymal stem cells (MSCs) to differentiate into vascular endothelia cells (ECs) in peritubular capillary (PTC) in chronic aristolochic acid nephropathy (CAAN).


METHODS
MSCs were isolated from a male Wistar rat. The surface markers were identified with flow cytometry. Thirty female Wistar rats were randomly divided into 3 equal groups: Group A, perfused intragastrically with decoction of Caulis Aristolochiae manshuriensis for 12 weeks to establish CAAN models, Group B, perfused intragastrically with decoction of Caulis Aristolochiae manshuriensis for 12 weeks to establish CAAN models and injected with the MSCs by caudal vein in the 12th week, and Group C, perfused intragastrically with drinking water for 12 weeks and then injected with normal saline by caudal vein to be used as normal controls. At week 16, specimens of blood and urine were collected to detect the blood urea nitrogen (BUN), serum creatinine (Scr) and urine protein, and then the rats were killed with their kidneys taken out. Sex-determining region of the Y chromosome-fluorescence in situ hybridization (SRY-FISH) test with carboxyfluorescein (FAM)- was used to detect the cells originated from the source of the male donors. Immunohistochemistry was used to detect CD34, marker antigen pf EC. HE and Masson staining and electron microscope were used to observe the pathology of the kidney. Immunohistochemistry and RT-PCR were used to detect the expression of vascular endothelial growth factor (VEGF). Correlation analysis was conducted to study the relationships among these indices.


RESULTS
Y chromosome and CD34 double positive cells could be seen in the renal tissue of Group B. At week 16, the density of PTC and integrated optical density of VEGF of Group A were (5.3 +/- 0.8)/0.13 mm2 and (2.8 +/- 0.4) x 10(3) respectively, both significantly lower than those of Group B [(26.5 +/- 1.6)/0.13 mm2 and (14.7 +/- 1.7) x 10(3) respectively, both P < 0.011]. The Scr and urine protein of Group A were significantly higher than those of Group B. The expression of VEGF mRNA of Group A was significantly lower than that of Group B.


CONCLUSIONS
MSCs can differentiate into ECs. MSCs transplantation has beneficial effects on CAAN, which is possibly related with the reduction of PTC.
Zou
Jie
J
Department of Nephrology, First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Feng
Jiang-Min
JM
Li
Wei
W
Guo
Wei
W
Wang
Li-Ning
LN
D000818:Animals; D034341:Aristolochic Acids / Q000633:toxicity; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D007674:Kidney Diseases / Q000139:chemically induced; D007684:Kidney Tubules / Q000098:blood supply; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar
D034341:Aristolochic Acids; C000228:aristolochic acid I