Efficacy of allogeneic mesenchymal stem cell administration in a model of acute ischemic kidney injury in cats.
OBJECTIVE
To evaluate the effects of allogeneic mesenchymal stem cells (MSCs) in a model of ischemic acute kidney injury (AKI).


METHODS
Randomized controlled trial.


METHODS
Adult, purpose-bred research cats (n=15) and a historical reference group (n=3).


METHODS
Cats underwent unilateral, in vivo, warm renal ischemia, then intravenous administration of 4 million adipose-derived MSCs, bone marrow-derived MSCs, or fibroblasts (n=5/treatment) 1h after reperfusion. Serum creatinine and blood urea nitrogen concentrations were measured at baseline and days 1 and 6. Urine specific gravity, urine protein to urine creatinine ratio, and glomerular filtration rate were measured at baseline and day 6. Both kidneys were harvested on day 6; histopathology was described and scored and smooth muscle actin was quantified with histomorphometry. A 2-way ANOVA was used to compare time and treatment. Chi square analysis was used to determine the % of cats with at least International Renal Interest Society (IRIS) Grade 1 AKI.


RESULTS
Time, but not treatment, had a significant effect on renal function. No difference was noted in % of cats with IRIS AKI. Significantly fewer mitotic figures were observed in ischemic kidneys that received bone-marrow derived MSCs vs. fibroblasts. No differences in smooth muscle actin staining were noted.


CONCLUSIONS
This study did not support the use of allogeneic MSCs in AKI in the regimen described here. Type of renal injury, MSC dose, allogenicity, duration, and route or timing of administration could influence the efficacy MSCs.
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, 2200 College Station Road, Athens, GA 30602, USA. Electronic address: ddross@uga.edu.
Desiree D
DD
Rosselli
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, 2200 College Station Road, Athens, GA 30602, USA. Electronic address: jmumaw@uga.edu.
Jennifer L
JL
Mumaw
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, 2200 College Station Road, Athens, GA 30602, USA. Electronic address: vannadvm@uga.edu.
Vanna
V
Dickerson
Georgia Veterinary Diagnostic Laboratory, College of Veterinary Medicine, University of Georgia, 501 DW Brooks Drive, Athens, GA 30602, USA. Electronic address: cathybro@uga.edu.
Cathy A
CA
Brown
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, 501 DW Brooks Drive, Athens, GA 30602, USA. Electronic address: sbrown01@uga.edu.
Scott A
SA
Brown
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, 2200 College Station Road, Athens, GA 30602, USA. Electronic address: cws@uga.edu.
Chad W
CW
Schmiedt
D058186:Acute Kidney Injury / Q000601:surgery*; D000273:Adipose Tissue / Q000166:cytology; D061605:Administration, Intravenous; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002415:Cats; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D014184:Transplantation, Homologous
Acute kidney injury; Allogeneic; Feline; Ischemia reperfusion; Mesenchymal stem cells