Abstract
BackgroundMesenchymal stem cells (MSCs) are derived from multiple tissues, including amniotic fluid (AF-MSCs) and the umbilical cord (UC-MSCs). Although the therapeutic effect of MSCs on sepsis is already known, researchers have not determined whether the cells from different sources require different therapeutic schedules or exert different curative effects. We assessed the biofunction of the administration of AF-MSCs and UC-MSCs in rats with caecal ligation and puncture (CLP)-induced sepsis.MethodsCLP was used to establish a disease model of sepsis in rats, and intravenous tail vein administration of AF-MSCs and UC-MSCs was performed to treat sepsis at 6 h after CLP. Two phases of animal experiments were implemented using MSCs harvested in saline with or without filtration. The curative effect was measured by determining the survival rate. Further effects were assessed by measuring proinflammatory cytokine levels, the plasma coagulation index, tissue histology and the pathology of the lung, liver and kidney.ResultsWe generated rats with medium-grade sepsis with a 30–40% survival rate to study the curative effects of AF-MSCs and UC-MSCs. MSCs reversed CLP-induced changes in proinflammatory cytokine levels and coagulation activation. MSCs ameliorated CLP-induced histological and pathological changes in the lung, liver and kidney. AF-MSCs and UC-MSCs functioned differently in different tissues; UC-MSCs performed well in reducing the upregulation of inflammatory cytokine levels in the lungs and inhibiting the inflammatory cell infiltration into the liver capsule, while AF-MSCs performed well in inhibiting cell death in the kidneys and reducing the plasma blood urea nitrogen (BUN) level, an indicator of renal function.ConclusionsOur studies suggest the safety and efficacy of AF-MSCs and UC-MSCs in the treatment of CLP-induced sepsis in rats and show that the cells potentially exert different curative effects on the main sepsis-affected tissues.
Highlights
Mesenchymal stem cells (MSCs) are derived from multiple tissues, including amniotic fluid (AF-MSCs) and the umbilical cord (UC-MSCs)
Sepsis is defined as a systemic inflammatory response syndrome (SIRS) that is induced by an infection, leading to an imbalance in the adaptive and innate immune systems in an individual
We provide evidence that intravenous tail vein injections of human amniotic fluid MSCs (AF-MSCs) and Umbilical cord-MSCs (UC-MSCs) are both therapeutic programmes that reduce mortality in rat models of caecal ligation and puncture (CLP)-induced sepsis
Summary
Mesenchymal stem cells (MSCs) are derived from multiple tissues, including amniotic fluid (AF-MSCs) and the umbilical cord (UC-MSCs). In the hyperinflammatory phase of sepsis, the innate and adaptive immune systems are activated to eliminate the pathogens causing the disease [2] Medical efforts such as the Surviving Sepsis guidelines [3] have been implemented to improve critical care, early detection and rapid intervention, resulting in a reduction in the mortality of sepsis in recent years, but the mortality rate is still approximately 20% [4, 5]. MSCs have become a topic of increasing interest in the scientific community because these cells are regarded as a potential tool in regenerative medicine and cell therapy They can be extracted from both healthy donors and patients and are expanded in vitro to a therapeutic volume without substantial ethical concern. The safety and efficacy of MSCs should be explicitly determined before their large-scale clinical application, and the study of MSC biofunction in sepsis pathology would benefit from acquiring an advanced application scheme for the clinical setting
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