Hypoxia pretreated MSC derived extracellular vesicles alleviate acute renal ischemia reperfusion injury mediated by anti-oxidative stress

Hypoxia pretreated mesenchymal stromal cell (MSC) and MSC derived extracellular vesicles (EVs) have shown a stronger capability for tissue ischemia-reperfusion injury (IRI) repair. However, the effect of hypoxia on MSC and MSC-EVs and their therapeutic effect on renal IRI remains unclear. Human umbilical cord MSC (hucMSC) was pretreated with hypoxia for 24h. The proliferation and the transcriptome of hucMSC was detected. EVs were quantified and characterized. In vivo, the therapeutic effectiveness of hucMSC-EVs in renal IRI was assessed through histological examination, serum creatinine and blood urea nitrogen levels. The apoptosis, proliferation, and angiogenesis of renal tissue were assessed. In vitro, renal tubular epithelia cells injury induced by antimycin A (AMA) in NRK-52E cells was used to prove the therapeutic effect of EVs. Hypoxia promotes MSC proliferation and EVs production. Hypoxia-derived MSC-EVs exhibit a more robust capacity to mitigate renal IRI. hucMSC-EVs effectively enhance the proliferation and anti-apoptotic capabilities of renal tubular epithelial cells, both in vivo and in vitro. The protein profiles of EVs revealed the accumulation of numerous anti-oxidative stress proteins, with GSTO1 being particularly prominent. And this anti-oxidative effect was diminished in rats treated with EVs knockdown of GSTO1.Our findings highlight that hypoxic EVs treatment effectively reduced oxidative stress in IRI kidneys, which can be a novel and promising therapeutic intervention for renal IRI.