Fig. 4.

Exosome-based therapy for renal IRI. A The renal IRI in miniature pigs was significantly reduced at 72 h after treatment. (i) Arrows point to injured tubules with intraluminal casts with H&E staining.. Scale bar = 100 µm. (ii) Serum creatinine (SCr) and BUN were significantly reduced, indicating improved renal function. (iii, iv, & v) IRI-induced expression and phosphorylation of MLKL were suppressed by exosomes. Scale bar = 200 µm. (vi) Arrows point to F4/80-positive macrophages. Scale bar = 100 µm. (vii) Counts of F4/80 positive cells [125]. B MSC-derived exosomes accumulated in renal tubules of IRI mice, mitigating damage by rescuing G2/M arrest and reducing apoptosis via inhibition of p53 signaling through miR-125b-5p. (i) DiD-labeled MSC-exos accumulated in renal tubules of renal IRI mice. (ii) Western blot of p53 in NC-exos or miR-125b-5p^IN-exos treated IRI mice. (iii) Confocal images of KIM-1 + positive tubules. (iv) Quantification of KIM-1 + tubules per high power field. Scale bars, 25 μm [124]. C Human primary renal tubular cell and exosome therapy mitigated rat renal IRI. (i) Serum creatinine levels. Sham (sham), untreated (saline), IRI rats treated with human kidney cells (huCells) and human exosomes (huEXO). At 48 h post-IRI, creatine level of huEXO group was significantly lower than huCells group. (ii) Kidney weights reduced after cell and exosome treatment. (iii) Oxidative stress, indicated by 4-hydroxynonenal adducts (brown), was substantially decreased following exosome therapy. (iv) Cellular attenuation and tubular dilation were improved in ISCH/CELLS and largely prevented in ISCH/EXO [129]. D Survival and renal function improved in rat IRI models treated with USC and USC-derived exosomes. (i) Survival rates significantly increased for both USC and USC-exosome groups. (ii) Decreased BUN and creatinine (Cr) levels indicated improved renal function [133]