Human umbilical cord-derived мesenchymal stromal cells mitigate lipopolysaccharide-induced liver injury in rats

Abstract

Acute Respiratory Distress Syndrome (ARDS) is a severe clinical condition that can cause multi-organ dysfunction, including liver injury. Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) have been shown to possess therapeutic potential for a variety of diseases due to their ability to differentiate into various cell types and their anti-inflammatory and immunomodulatory properties. Purpose: To investigate the potential of hUC-MSCs for treating lipopolysaccharide (LPS)-induced liver injury in rats. Materials and methods: 72 mature male Wistar rats were randomly assigned to nine groups: control, 3 days, 7 days, and 28 days after intranasal administration of LPS, 24 hours of LPS and 2 days of hUC-MSCs, 4 days of LPS and 3 days of hUC-MSCs, 14 days of LPS and 14 days of hUC-MSCs, 21 days of LPS and 7 days of hUC-MSCs injection, and control 3 days after hUC-MSCs injection. The isolation of MSCs from human umbilical cord tissue was performed using an enzymatic digestion method with collagenase I. hUC-MSCs were injected intraperitoneally at a dose of 1∙106 cells/kg body weight. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were measured using the kinetic method. The levels of hepatocellular necrosis, liver structural damage, hepatocyte vacuolation, inflammation and disseminated intravascular coagulation (DIC) were analyzed by histological scoring of sections stained with hematoxylin and eosin. The expression of TGF-β1 in the liver tissue was evaluated by immunohistochemistry. Results: The preclinical study demonstrated that treatment with hUC-MSCs significantly improved liver function and attenuated LPS-induced liver injury in rats. This was evidenced by a reduction in hepatocellular necrosis, liver structural damage, hepatocyte vacuolation, inflammation, signs of DIC, fibrosis and lower levels of serum liver markers ALT, AST and ALP in the hUC-MSCs-treated groups compared to the untreated groups. The study also revealed that the use of hUC-MSCs was more effective at the earlier stage of liver injury. Conclusions: Our findings suggest that hUC-MSCs therapy may hold promise as a potential treatment for LPS-induced liver injury. Further research is needed to better understand the underlying mechanisms and to determine the potential for hUC-MSCs therapy in clinical practice.