Anti-Fibrotic and Regenerative Potential of Mesenchymal Stem Cell-Derived Exosomes in Cisplatin-Induced Kidney Injury

Authors : Halime Tozak Yıldız, Kübra Tuğçe Kalkan, Numan Baydilli, Zeynep Burcin Gonen, Ozge Cengiz Mat, Eda Köseoğlu, Gözde Özge Önder, Arzu Yay

Pages : 223-231

Doi:10.32708/uutfd.1691390

View : 72 | Download : 87

Publication Date : 2025-08-28

Article Type : Research Paper

Abstract :Cisplatin is a widely used chemotherapeutic agent with potent antitumor activity; however, its nephrotoxicity limits clinical use, affecting 30–40% of treated patients. This study aimed to investigate the effects of mesenchymal stem cell-derived exosomes on cisplatin-induced nephrotoxicity and fibrosis in rat kidney tissue. Rats were divided into Control, Cis, Exo, and Cis+Exo groups. Nephrotoxicity was induced by a single dose Cis. Exosomes were isolated using a commercial kit and characterized by nanoparticle tracking analysis. Histopathological evaluations were performed Hematoxylin&Eosin and Periodic Acid-Schiff. Fibrosis markers were assessed by immunohistochemistry. Statistical analyses were conducted using one-way ANOVA and Kruskal-Wallis tests with Bonferroni and Dunn’s post-hoc tests, considering p<0.05 as statistically significant. In the Cis group, significant tubular degeneration, necrosis, and fibrosis were observed compared to the Control group. TGF-β1, α-SMA, and TLR-4 expressions were markedly increased in the Cis group (p<0.001). Exo treatment significantly reduced the expression levels of these fibrosis markers compared to the Cis group (TGF-β1 and TLR-4, p<0.001; α-SMA, p<0.05). Histopathological analysis revealed that Exo administration mitigated nephrotoxic damage and supported tissue regeneration, with tissue architecture resembling that of the Control group. This study demonstrates that MSC-derived exosomes alleviate not only acute cisplatin-induced injury but also the associated fibrotic response. A single dose of exosome treatment significantly modulated the fibrotic response and reduced oxidative stress-induced damage. These findings indicate that MSC-derived exosomes, known for their regenerative and tissue-repairing properties, also possess significant potential as antifibrotic therapeutic agents, highlighting the need for further research toward clinical applications.
Keywords : eksozom, fibrozis, mezenkimal kök hücre, nefrotosisite, sisplatin.

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