Exosomes are membrane-enclosed vesicles secreted by cells, containing a variety of biologically active ingredients including
proteins,
nucleic acids and
lipids. In this study, we investigated the
therapeutic effects of the exosomes and underlying mechanisms in a miniature pig model of
ischemia/reperfusion-induced
acute kidney injury (I/R-AKI). The exosomes were extracted from cultured human umbilical cord derived mesenchymal stem cells (hUC-MSCs) and infused into a miniature pig model of I/R AKI. Our results showed that 120 min of unilateral
ischemia followed by reperfusion and contralateral
nephrectomy resulted in renal dysfunction, severe kidney damage, apoptosis and necroptosis.
Intravenous infusion of one dose of exosomes collected from about 4 × 108 hUC-MSCs significantly improved renal function and reduced apoptosis and necroptosis. Administration of hUC-MSC exosomes also reduced the expression of some pro-inflammatory
cytokines/
chemokines, decreased infiltration of macrophages to the injured kidneys and suppressed the phosphorylation of nuclear factor-κB and
signal transducer and activator of transcription 3, two transcriptional factors related to inflammatory regulation. Moreover, hUC-MSC exosomes could promote proliferation of renal tubular cells, angiogenesis and upregulation of Klotho and
Bone Morphogenetic Protein 7, two renoprotective molecules and
vascular endothelial growth factor A and its receptor. Collectively, our results suggest that injection of hUC-MSC exosomes could ameliorate I/R-AKI and accelerate renal tubular cell repair and regeneration, and that hUC-MSC exosomes may be used as a potential
biological therapy for
Acute kidney injury patients.