Bone Marrow-Derived Mesenchymal Stem Cells Repaired but Did Not Prevent Gentamicin-Induced Acute Kidney Injury through Paracrine Effects in Rats

Abstract

This study evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) or their conditioned medium (CM) on the repair and prevention of Acute Kidney Injury (AKI) induced by gentamicin (G). Animals received daily injections of G up to 20 days. On the 10th day, injections of BMSCs, CM, CM+trypsin, CM+RNase or exosome-like microvesicles extracted from the CM were administered. In the prevention groups, the animals received the BMSCs 24 h before or on the 5th day of G treatment. Creatinine (Cr), urea (U), FENa and cytokines were quantified. The kidneys were evaluated using hematoxylin/eosin staining and immunohystochemistry. The levels of Cr, U and FENa increased during all the periods of G treatment. The BMSC transplantation, its CM or exosome injections inhibited the increase in Cr, U, FENa, necrosis, apoptosis and also increased cell proliferation. The pro-inflammatory cytokines decreased while the anti-inflammatory cytokines increased compared to G. When the CM or its exosomes were incubated with RNase (but not trypsin), these effects were blunted. The Y chromosome was not observed in the 24-h prevention group, but it persisted in the kidney for all of the periods analyzed, suggesting that the injury is necessary for the docking and maintenance of BMSCs in the kidney. In conclusion, the BMSCs and CM minimized the G-induced renal damage through paracrine effects, most likely through the RNA carried by the exosome-like microvesicles. The use of the CM from BMSCs can be a potential therapeutic tool for this type of nephrotoxicity, allowing for the avoidance of cell transplantations.

Extracellular Vesicles in Renal Diseases

“…63 A similar finding was described in a gentamicin-induced model of AKI. 64 The therapeutic effect of EVs from other types of stem cells has also been described. 65 Injection of EVs derived from endothelial progenitor cells in a rat model of AKI (ischemia reperfusion Column 2 shows scatter of the laser of these same cells seen in column 1.…”

Bone marrow-derived mesenchymal stem cells attenuate acute liver injury and regulate the expression of fibrinogen-like-protein 1 and signal transducer and activator of transcription 3

“…Bone-marrow-derived mesenchymal stem cells (BMSCs) have been reported to be able to treat numerous types of disease in animals, including acute kidney failure (8), ischemic heart disease (9), lung injury (10) and intracerebral hemorrhage (11) tissues in response to damage, including necrosis (12), hypoxia (13) and ischemia (14). The mechanisms by which BMSCs alleviate acute liver injury involve challenges.…”

Role of Mesenchymal Stem Cells Versus their Conditioned Medium on Cisplatin-Induced Acute Kidney Injury in Albino Rat. A Histological and Immunohistochemical Study

“…Similar results were recorded by previous investigators [13] , who stated that even after administration of high consecutive doses of CM, no improvement had been observed in animal models of ischemia reperfusion kidney injury. On the contrary, other researchers reported that CM improved renal function and increased survival in AKI experimental models [37] .…”

“…Treatment of animals with these exosomes significantly induced cellular proliferation and inhibited the tubular necrosis [37] .…”