Mesenchymal stem cell-derived microvesicles versus sodium glucose cotransporter-2 inhibitors in ameliorating acute renal cortical injury of ischemia reperfusion rat model

Abstract

Acute kidney injury (AKI) is primarily caused by renal ischemia/reperfusion (I/R) injury, which is clinically linked to significant morbidity and death in both developed and developing countries. Therefore, the aim of this work is to compare the possible ameliorative effect of dapagliflozin (DAPA) versus human umbilical cord mesenchymal stem cells derived microvesicles (HUC-MSC-MVs) through biochemical, light, and electron microscope studies. Fifty-six adult male albino rats were divided into four groups: control, I/R, I/R+DAPA, and I/R+MVs groups. Both serum and tissue samples were collected for biochemical analysis. Renal specimens were processed to evaluate the histological structure, collagen content, desmin, and β-catenin immune expression. Morphometric and statistical analyses were performed. I/R group revealed prominent histoarchitectural alterations and a significant rise in the serum urea, creatinine, oxidative stress markers, and inflammatory mediators. Alterations were partially attenuated by DAPA therapy, whereas HUC-MSC-MVs significantly improved all parameters. We concluded that MSC-MVs administration exert a more significant ameliorative effect comparing to DAPA therapy via attenuating the oxidative stress and inflammation in addition to, restoring angiogenesis and cell proliferation. However, these findings remain preclinical and further researches are acclaimed for dose optimization, safety evaluation, and clinical validation before application in human AKI.