Exploring the Therapeutic Role of Human Stem Cell-derived Extracellular Vesicles in a Mouse Model of Adriamycin-Induced Chronic Glomerulonephritis

Focal segmental glomerulosclerosis (FSGS), one of the most common causes primary glomerular disease in adults, is characterized by podocyte injury and progressive glomerular damage. Current treatment strategies remain inadequate, underscoring the need for novel therapeutic approaches. Recent studies suggest that stem cell-derived extracellular vesicles (EVs) might offer a promising alternative due to their regenerative properties and ability to mitigate inflammation. This study aims to evaluate the therapeutic potential of liver mesenchymal stromal cell-derived EVs (L-MSC-EVs) in a mouse model of FSGS, induced by Adriamycin (ADR), a toxic drug. L-MSC-EVs have been isolated using differential ultracentrifugation and their efficacy has been assessed by treating ADR-induced FSGS mice with L-MSC-EVs and comparing the outcomes to the only-ADR treated control mice. Results highlited that L-MSC-EV treatment led to significant improvements in kidney function, as evidenced by reductions in both albumin and total protein levels in urines, togheter with a reduction in plasma levels of urea nitrogen (BUN) and creatinine. Preliminary morphological analyses revealed a decreased collagen deposition in EVs-treated mice compared to controls. Overall, these findings suggest that L-MSC-EVs attenuate renal damage by enhancing the overall kidney function and reducing fibrosis of the FSGS mouse model. In conclusion, L-MSC-EVs could be considered a promising therapeutic tool for the management of FSGS, supporting also further investigation into EV-based therapies as a novel therapeutic approach that can be extended to other chronic kidney diseases.