Desiree D Rosselli1, Jennifer L Mumaw2, Vanna Dickerson3, Cathy A Brown4, Scott A Brown5, Chad W Schmiedt6. 1. 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. 2. 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. 3. 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. 4. Georgia Veterinary Diagnostic Laboratory, College of Veterinary Medicine, University of Georgia, 501 DW Brooks Drive, Athens, GA 30602, USA. Electronic address: cathybro@uga.edu. 5. 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. 6. 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.
Abstract
OBJECTIVE: To evaluate the effects of allogeneic mesenchymal stem cells (MSCs) in a model of ischemic acute kidney injury (AKI). STUDY DESIGN: Randomized controlled trial. ANIMALS: Adult, purpose-bred research cats (n=15) and a historical reference group (n=3).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.
OBJECTIVE: To evaluate the effects of allogeneic mesenchymal stem cells (MSCs) in a model of ischemic acute kidney injury (AKI). STUDY DESIGN: Randomized controlled trial. ANIMALS: 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 ureanitrogen 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.
Authors: Boaz Arzi; Kaitlin C Clark; Ayswarya Sundaram; Mathieu Spriet; Frank J M Verstraete; Naomi J Walker; Megan R Loscar; Nasim Fazel; William J Murphy; Natalia Vapniarsky; Dori L Borjesson Journal: Stem Cells Transl Med Date: 2017-06-15 Impact factor: 6.940
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