Mesenchymal stem cells transplantation mildly ameliorates experimental diabetic nephropathy in rats.
BACKGROUND
Diabetic nephropathy is a common complication of diabetes mellitus. This study aimed to explore whether mesenchymal stem cells (MSCs) transplantation could attenuate diabetic nephropathy in experimental diabetic rats.


METHODS
Sprague-Dawley rats received a single intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). Diabetic rats were randomized to four groups: diabetes control group (DC), ciclosporin A group (CsA), MSC group, and MSC + CsA group (MSCA). Bone marrow mesenchymal stem cells were cultured, identified and labeled by 5-bromo-2'-deoxyuridine (BrdU) in vitro. Then they were transplanted to diabetic rats via introcardiac infusion. Ciclosporin A was administered daily at 5 mg/kg. At 1, 2, 4, 8 weeks after transplantation, random blood glucose, urine albumin/creatinine ratio (Alb/Cr), endogenous creatinine clearance rate and renal mass index were tested. Renal morphology and labeled cells were examined.


RESULTS
Cultured MSCs expressed mesenchymal cell phenotype, and could be multidifferentiated to osteogenic and adipogenic cells. Labeled MSCs could be detected in the kidney of nephropathic rats, mainly in renal interstitium, but they did not propagate after engrafting in kidney. Over the course of the experiment, MSCA group showed a significant decrease in blood glucose compared with MSC group, CsA group and DC group (P < 0.05, respectively). The Alb/Cr in MSCA group and MSC group were significantly lower than CsA group and DC group (P < 0.05). And the Alb/Cr in MSCA group showed a significant decrease compared with MSC group (0.74 vs 0.84, P < 0.05). There was a significant difference in renal mass index between the MSCA group and DC group (5.66 vs 6.37, P < 0.05). No significant difference was found in creatinine clearance rate among 4 groups (P > 0.05). Treatment with MSC + CsA significantly ameliorated the morphology of diabetic kidney.


CONCLUSIONS
MSC could mildly ameliorate diabetic nephropathy by decreasing blood glucose, Alb/Cr ratio and renal mass index.
Zhou
Hong
H
Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
Tian
Hao-ming
HM
Long
Yang
Y
Zhang
Xiang-xun
XX
Zhong
Li
L
Deng
Li
L
Chen
Xiao-he
XH
Li
Xiu-qun
XQ
D000818:Animals; D001786:Blood Glucose; D003928:Diabetic Nephropathies / Q000097:blood / Q000378:metabolism / Q000628:therapy*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008853:Microscopy; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose