title: Assessment of intravenous adipose-derived allogeneic mesenchymal stem cells for the treatment of feline chronic kidney disease: a randomized, placebo-controlled clinical trial in eight cats.
abstract: OBJECTIVE
  Feline chronic kidney disease (CKD) is characterized by chronic tubulointerstitial nephritis, and inflammation contributes to the progression of renal fibrosis. Mesenchymal stem cells (MSCs) have demonstrated anti-inflammatory and antifibrotic effects in rodent CKD models. However, few randomized trials evaluating the effectiveness of MSC therapy for diseases in companion animals have been reported. The purpose of this study was to evaluate the effectiveness of allogeneic MSCs for the treatment of feline CKD using a randomized, placebo-controlled trial.
  
  
  METHODS
  MSCs were isolated from the cryopreserved adipose tissues of specific pathogen-free research cats and culture expanded. CKD cats were enrolled in a randomized, placebo-controlled, blinded one-way crossover clinical study. Four CKD cats were randomized to receive 2 × 10(6) MSCs/kg intravenously at 2, 4 and 6 weeks. Four CKD cats were randomized to receive placebo, with two cats crossing over to the MSC treatment group and one cat failing to complete the trial. Complete blood counts, chemistry and urinalysis were performed at weeks 0, 2, 4, 6 and 8. Glomerular filtration rate (GFR) via nuclear scintigraphy and urine protein:creatinine ratio (UPC) were determined at weeks 0 and 8.
  
  
  RESULTS
  Six cats received three doses of allogeneic MSC culture expanded from cryopreserved adipose without adverse effects. No significant change in serum creatinine, blood urea nitrogen, potassium, phosphorus, GFR by nuclear scintigraphy, UPC or packed cell volume was seen in cats treated with MSCs. Individual changes in GFR were 12%, 8%, 8%, 2%, -13% and -67% in treated cats compared with 16%, 36% and 0% in placebo-treated cats.
  
  
  CONCLUSIONS
  While administration of MSC culture expanded from cryopreserved adipose was not associated with adverse effects, significant improvement in renal function was not observed immediately after administration. Long-term follow-up is necessary to determine whether MSC administration affects disease progression in cats with CKD.
authors.affiliation: Center for Immune and Regenerative Medicine, Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA jquimby@colostate.edu.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Quimby
authors.affiliation: Center for Immune and Regenerative Medicine, Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Webb
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: Elissa
authors.initials: E
authors.lastname: Randall
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Marolf
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA Current address: AV Veterinary Radiology, Denver, CO 80202, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Valdes-Martinez
authors.affiliation: Center for Immune and Regenerative Medicine, Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: Steve W
authors.initials: SW
authors.lastname: Dow
mesh_terms: D000273:Adipose Tissue / Q000601:surgery; D000818:Animals; D001806:Blood Urea Nitrogen; D002371:Cat Diseases / Q000601:surgery*; D002415:Cats; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate / Q000662:veterinary; D007677:Kidney Function Tests / Q000662:veterinary; D045164:Mesenchymal Stem Cell Transplantation / Q000662:veterinary*; D059630:Mesenchymal Stem Cells; D051436:Renal Insufficiency, Chronic / Q000601:surgery / Q000662:veterinary*