#5978 SUBCAPSULAR INJECTION OF EXTRACELLULAR VESICLES FROM MESENCHYMAL STEM CELLS, PROMOTED ADDITIONAL RENOPROTECTION IN AN EXPERIMENTAL MODEL OF CKD

Abstract Background and Aims Chronic kidney disease (CKD) is considered a public health concern worldwide, both due to its insidious highly debilitating feature high global prevalence. Clinical management of CKD often achieved by the blockade renin-angiotensin-aldosterone system (RAAS). However, this treatment alone not efficient prevent progression completely, motivating scientific community search for alternative treatments control detain evolution end-stage renal failure. In context, we have recently shown that association single subcapsular injection 2 × 106 adipose-derived mesenchymal stem cells (ASC) RAAS with AT1RB Losartan (LOS) promoted greater renoprotection when compared LOS monotherapy, leading normalization urinary protein excretion (UPE) regression established glomerulosclerosis (GS), in experimental CKD. Since there are methodological limits number ASC can be injected under capsule, based on current literature, which suggests main beneficial effects direct situ cell differentiation, but paracrine factors produced released ASC; present study aimed investigate if extracellular vesicles (EV) derived from ASC, oral would promote additional renoprotective model Method The protocol was approved Ethics Committee Use Experimental Animals University São Paulo Medical School (CEUA-FMUSP No 1761/2022). EV were obtained isolated gonadal adipose tissue 5 male Wistar rats. Cells cultured until P4, characterized flow cytometry vitro kept serum deprivation 24 h. conditioned culture media, containing these cells, ultracentrifuged resulting pellets diluted 100 μL sterile PBS used injections. induced 25 rats through surgical ligation 3 branches left artery, followed total nephrectomy right kidney, 5/6 ablation. Additional 10 Sham-operated as control. After 15 days surgery, animals submitted ablation stratified into groups, closely similar mean values body weight (BW), systolic blood pressure (SBP), UPE albumin (UAE), before start different treatments. group untreated, LOS+EV received diary 50 mg/Kg/d Losartan, drinking water underwent second surgery application EV. All 30 after induction, BW, SBP, UAE analyzed again. where then euthanized assessment creatinine (SCr) urea nitrogen (BUN) concentration, well histological studies determine percentage GS interstitial infiltration macrophages (CD68). Results LOS, significantly improved antihypertensive drug. CKD+LOS+EV exhibited normal spite having only 1/6 functioning mass. Moreover, combined reduced numerically diminished de glomerulosclerosis, alone. Detailed results presented Table 1. Data Mean ± SE. Differences among groups one-way ANOVA: p<0.05 vs.*CONT, #CKD, †LOS. Conclusion Despite small group, our preliminary suggest exert associated especially regarding SBP protection glomerular filtration barrier integrity.