Umbilical Cord Mesenchymal Stem Cell Exosomes Alleviate the Progression of Kidney Failure by Modulating Inflammatory Responses and Oxidative Stress in an Ischemia-Reperfusion Mice Model

Abstract

The efficacy of stem cells for the treatment of renal failure is widely recognized; however, an excessive volume of stem cells can block the capillaries; thus, the potential risks should not be ignored. Stem cell exosomes are secretory extracellular vesicles with a size of 30–150 nm, which have similar functions to stem cells but are much smaller in size. This study aims to investigate the role of human umbilical cord mesenchymal stem cells (UCMSCs)-derived exosomes in the treatment of renal failure caused by ischemia-reperfusion. Fifty 8-week-old female C57 mice underwent bilateral renal ischemia-reperfusion surgery for 30 minutes. After 4 weeks, the treated group received UCMSCs-derived exosomes treatment, and the control group was solely injected with the same amount of PBS. At the age of 16 weeks, the kidney function, kidney damage, inflammatory responses and oxidative stress were measured. Moreover, the effect of UCMSCs-derived exosomes on the phenotype of M1 macrophages was also tested. The results showed that UCMSCsderived exosomes significantly reduced the levels of blood urea nitrogen (BUN), serum creatinine (SCR), and urinary albumin and creatinine (ACR) and 8-isoprostane. UCMSCs-derived exosomes also improved the atrophy of the kidney and glomerulus, decreased kidney pro-inflammatory factors expression (mRNA of II-1β, II-6, Tnf-α, and Mcp-1) and oxidative stress (malondialdehyde), and increased glutathione level. However, F4/80 immunohistochemistry did not show significant differences between the two groups. In systemic inflammation measurement, UCMSCs-derived exosomes decreased proinflammatory factors TNF-α, IL-6, and IL-1β levels, and increased anti-inflammatory factor IL-10 level. In vitro experiments showed that UCMSCs-derived exosomes decreased the protein expression level of TNF-α and increased the protein expression level of IL-10 in M1 macrophages. UCMSCs-derived exosomes reduce kidney inflammation and oxidative stress by improving systemic inflammation, and thus reduce kidney damage and improve kidney function. This study shows the potential application value of exosomes in the treatment of renal failure.

Tibetan Medicine Shi-Wei-Gan-Ning-San Alleviates Carbon Tetrachloride-Induced Chronic Liver Injury by Inhibiting TGF-β1 in Wistar Rats

“…Previous studies have demonstrated that excessive inammation and ROS are important causes of liver injury, and inhibiting in ammation and ROS can e ectively alleviate liver injury [38][39][40][41][42]. Especially in the CCl 4 -induced liver injury model, several studies indicate that natural products can alleviate tissue injury by modulating immune responses and oxidative stress [43][44][45][46].…”

Mesenchymal Stem Cell Therapy in Kidney Diseases: Potential and Challenges

“…For instance, Zhang et al 132 revealed that human Wharton’s jelly MSCs-EVs could protect the kidney against IRI by mitigating oxidative stress. Another study confirmed that exosomes derived from UCMSCs prevented AKI progression via suppressing renal oxidative stress and inflammation as well as improving kidney function of kidney failure 48 . Cao et al 133 showed that human placenta MSCs-Exo reduced oxidative stress and mitochondrial fragmentation in a renal IRI model through activation of the Nrf2/keap1 pathway.…”

Human umbilical cord mesenchymal stem cells-derived exosomes for treating traumatic pancreatitis in rats

“…Significantly, hucMSC-Exs have been reported to exert protective effects in diseases of liver and lungs, kidney injury, as well as in diabetes [20][21][22]. A study showed that hucMSC-Exs improved glomerular atrophy by reducing blood urea nitrogen (BUN), serum creatinine (SCR), and urinary albumin levels, and reduced inflammation and oxidative stress by ameliorating systemic inflammation to repair renal injury and improve renal function [23]. Another study reported that hucMSC-Exs decreased alveolar damage and inflammatory response, and increased the proportion of M2 macrophages in the mice model of systemic lupus erythematosus [24].…”