Adipose-Derived Mesenchymal Stem Cells Improved Acute Renal Failure Induced by Ischemia–Reperfusion Injury: Focusing on Toll-Like Receptor 4 Activity and Endoplasmic Reticulum Stress Response Publisher Pubmed



Hafazeh L ; Kadkhodaee M ; Seifi B ; Akhondzadeh F ; Azedi F ; Noori H ; Hajiaqaei M ; Ranjbaran M
Source: Journal of Physiology and Biochemistry Published:2026

Abstract

This study evaluated the efficacy of adipose-derived mesenchymal stem cells (AD-MSCs) in reducing pathological alterations linked to acute kidney injury (AKI) caused by ischemia–reperfusion injury (IRI). In this study, 18 male rats were divided into three groups: Sham, IRI, and IRI + AD-MSC. IRI was induced by clamping the renal pedicles for 45 min, while the Sham group animals underwent the same surgical procedure without vascular clamping. In the IRI + AD-MSC groups, immediately after clamp removal, the animals received an intraperitoneal injection of 1 × 10⁶ AD-MSCs. To enable tracking, AD-MSCs were transfected with green fluorescent protein (GFP). The distribution of these labeled cells was examined at 24 and 48 h post-transplantation in three additional rats. Forty-eight hours after reperfusion, serum and kidney tissue samples were collected. The labeled AD-MSCs were more widely distributed in the injured kidney area of the IRI + AD-MSC group compared to the control group. In the group treated with AD-MSCs, there were notable reductions in serum blood urea nitrogen (BUN) and creatinine levels (P < 0.001), along with improvements in renal tissue damage and oxidative stress (P < 0.01). Additionally, the IRI + AD-MSC group showed significant decreases in toll-like receptor-4 (TLR4) protein levels (P < 0.01) and pro-inflammatory factors (P < 0.001), as well as reduced levels of endoplasmic reticulum (ER) stress proteins compared to the IRI group. This study suggested that AD-MSCs administration alleviates AKI, possibly by modulating TLR4 activity, decreasing inflammation, and reducing ER stress. © The Author(s) under exclusive licence to University of Navarra 2026.