Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.899869
Keywords
exosomes; ischemia; reperfusion; acute kidney injury; human umbilical cord derived mesenchymal stem cells; apoptosis; necroptosis; transcriptional factors; macrophages
Categories
Ask authors/readers for more resources
This study investigated the therapeutic effects and mechanisms of exosomes in a miniature pig model of I/R-AKI. The findings showed that infusion of hUC-MSC exosomes improved renal function, reduced cell apoptosis and necroptosis, suppressed inflammation, and promoted renal tubular cell repair and regeneration.
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 x 10(8) 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-kappa B 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available