Abstract
Acute respiratory distress syndrome (ARDS) is a severe pathological condition often accompanied by kidney injury. It is known that mesenchymal stem cells (MSCs) have high potential for treating various diseases due to their ability to paracrinely stimulate the regeneration of damaged cells and tissues and restore impaired organ functions. Purpose: To investigate the nephroprotective effect of human umbilical cord MSCs in a model of ARDS induced in rats by intranasal administration of lipopolysaccharide (LPS). Materials and methods: Seventy-two sexually mature male Wistar rats were randomly divided into nine groups: intact animals, 3 days, 7 days, and 28 days of ARDS development, MSC control, and four treatment groups: 24 hours LPS + 2 days MSCs, 4 days LPS + 3 days MSCs, 14 days LPS + 14 days MSCs, 21 days LPS + 7 days MSCs. MSCs were administered intraperitoneally at a dose of 106 cells/kg body weight. Levels of structural kidney damage were assessed using histological analysis of sections stained with hematoxylin and eosin. The expression of the fibrosis marker TGF-β1 in kidney tissues was evaluated by immunohistochemistry technique. Creatinine, urea, and uric acid levels in blood serum were measured using a kinetic method. Results: The conducted studies revealed the presence of significant damage to the kidney parenchyma, signs of fibrosis, and impaired nephron function in rats with modeled ARDS. The severity of pathological changes increased with the duration of the experiment. The use of human umbilical MSCs as a treatment factor significantly reduced the severity of coagulopathy, tubular necrosis, and destruction of renal corpuscles, inhibited the development of interstitial fibrosis, and improved the levels of renal blood markers. The best nephroprotective effect of MSCs was observed on the 28th day of the experiment in the group 14 daysLPS + 14 daysMSCs. This is likely due to the earlier use and longer duration of action of the stem cells compared to the group 21 daysLPS + 7 daysMSCs. Conclusion: Human umbilical MSCs have regenerative, antifibrotic, and nephroprotective effects in an animal model of kidney injury caused by ARDS. This may indicate the therapeutic potential of umbilical MSCs for the treatment of nephropathies of various origins.
Publisher
Institute of Cell Therapy
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