Efficacy Of Allogeneic Feline ADMSCs In The Treatment Of Cat Post-acute Renal Injury Models

Kidney is one of the most important metabolic organs in the body,which can purify metabolites and remove toxic substances entering the body.Kidney damage occurs when the kidneys become abnormal for a variety of reasons.At present,the clinical treatment of cat postrenal acute kidney injury(PR-AKI)is mainly diuresing,massive perfusion,discharging nitrogenous waste,reducing CRE and BUN.However,the therapeutic effect of this method is not very ideal,so it is meaningful to seek a more efficient treatment that can improve the chance of recovery.Adipose mesenchymal stem cells(ADMSCs)have low immunogenicity and have been proven to be useful in the treatment and repair of many diseases.Therefore,the use of ADMSCs is a very valuable treatment.Based on these theoretical basis,we established an animal model of cat PR-AKI,exploring the therapeutic effect of ADMSCs on acute kidney injury(AKI)by intravenous injection,and screened substances closely related to AKI through plasma metabonomics analysis of animal models.The cats were randomly divided into two groups:ADMSCs treatment group and control treatment group.The control treatment group was given anti-inflammatory drugs(cefotirome sodium,5 mg/kg),energy fluid(5%glucose injection)and 0.9%sodium chloride injection.In addition to the same liquid as the control treatment group,10 million units of ADMSCs were injected intravenously.Then,the experimental animals were subjected to biochemical examination,kidney B-ultrasonography,section analysis and metabonomics analysis.The results are as follows:(1)After animal models established,CRE index reached 770μmol/L,and other biochemical indexes(BUN,P and K~+)also showed obvious abnormalities.The clinical symptoms showed vomiting and lethargy,which were consistent with the clinical cases.Blood routine examination indicated bacterial infection and a certain degree of dehydration,but no other abnormalities were observed.B-ultrasonography showed obvious renal enlargement and ureteral dilation.Histological examination of the kidney showed obvious lesions with extensive congestion and inflammatory lesions.(2)Metabolomics tests of cat plasma between two groups,and 13 metabolites closely related to AKI were found through KEGG pathway analysis of differential metabolites:Carnosine,Melibiose,L-Palmitoyl carnitine,D-Glucosamine,3-Methylhistidine,4-Trimethylammonio butanoic acid,Saccharopine,Carnitine,Tyrosine,Arginine,Dihydroorotic acid,and Cytidine,Stachyose.(3)In the treatment,the recovery efficiency of CRE,BUN and P in ADMSCs group was faster than control treatment group.Especially,the recovery rate of CRE and BUN,the two most important indicators,was 12-24 h faster than control treatment group.In the ADMSCs group,leukocytes decreased rapidly in the first 24 h,but then showed a rebound phenomenon and increased rapidly,while in the control treatment group,leukocytes decreased slowly.In terms of clinical manifestations,all the cats in the ADMSCs group stopped vomiting on the first day of treatment,and the improvement of urine color was faster than control treatment group.The temperature of the cats in the ADMSCs group increased after the injection of stem cells,which was significantly different from control treatment group.B-ultrasound showed that the morphology of the kidney had recovered after treatment,but it had not yet returned to its normal size.In conclusion,this study demonstrated that intravenous transplantation of ADMSCs can significantly treat PR-AKI in cats,and identified 13 new markers or potential therapeutic targets for AKI.Our findings will provide new clues for improving clinical outcomes and outcomes in patients with AKI.