Use of mesenchymal stem cells and darbepoetin improve ischemia-induced acute kidney injury outcomes.
BACKGROUND
Interest has recently been focused on the possible role of bone marrow-originating stem cells and the therapeutic role of erythropoietin in the recovery of ischemia-induced acute kidney injury (AKI). The aim of the present study was to compare treatment with mesenchymal stem cells (MSCs) to treatment with darbepoetin-α (DPO) or both concomitantly in a rat model of ischemia/reperfusion (I/R) AKI.


METHODS
Forty male Sprague-Dawley rats were included, and 28 of them were randomly assigned to controls (treated with serum physiologic) or one of the three treatment groups treated with either DPO, MSCs, or both (MSCs and DPO concomitantly) after the induction of I/R injury. Hematocrit, serum creatinine, and BUN levels were obtained at 0, 24, 48, and 72 h of surgery, and renal tissue was obtained at 72 h after nephrectomy for histological analysis. Tissue injury was quantified by standardized histological scoring systems, using light and electron microscopes.


RESULTS
Treatment with MSCs or DPO improved renal function compared with controls. However, the improvement observed in renal function in the MSC/DPO group was better than that in the other groups. Histological analysis demonstrated that tissue injury was significantly decreased in rats in the MSC or DPO groups compared to that of the controls; however the best recovery was observed in rats treated with MSCs and DPO concomitantly.


CONCLUSIONS
These results suggest that concomitant application of DPO and MSCs may be a potential novel renoprotective therapy for patients after having sustained an ischemic renal insult.
Department of Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Bulent
B
Altun
Rahmi
R
Yilmaz
Tuncay
T
Aki
Hadim
H
Akoglu
Dilara
D
Zeybek
Serhan
S
Piskinpasa
Duygu
D
Uckan
Nuhan
N
Purali
Petek
P
Korkusuz
Cetin
C
Turgan
D058186:Acute Kidney Injury / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis; D001806:Blood Urea Nitrogen; D003131:Combined Modality Therapy; D003404:Creatinine / Q000097:blood; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006397:Hematinics / Q000627:therapeutic use*; D006400:Hematocrit; D007511:Ischemia / Q000150:complications; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications
D006397:Hematinics; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D003404:Creatinine