Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses.

Both high mobility group box-1 (HMGB1) and histones are major damage-associated molecular patterns (DAPMs) that mediate lethal systemic inflammation, activation of the complement and coagulation system, endothelial injury and multiple organ dysfunction syndrome in critical illnesses. Although accumulating evidence collectively shows that targeting HMGB1 or histones by their specific antibodies or inhibitors could significantly mitigate aberrant immune responses in multiple critically ill animal models, routine clinical use of such agents is still not recommended by any guideline. In contrast, extracorporeal blood purification, which has been widely used to replace dysfunctional organs and remove exogenous or endogenous toxins in intensive care units, may also exert an immunomodulatory effect by eliminating inflammatory mediators such as cytokines, endotoxin, HMGB1 and histones in patients with critical illnesses. In this review, we summarize the multiple immunopathological roles of HMGB1 and histones in mediating inflammation, immune thrombosis and organ dysfunction and discuss the rationale for the removal of these DAMPs using various hemofilters. The latest preclinical and clinical evidence for the use of extracorporeal blood purification to improve the clinical outcome of critically ill patients by targeting circulating HMGB1 and histones is also gathered.

Utilization of Hydrogels in Mesenchymal Stem Cell-Based Therapy for Kidney Diseases.

Kidney diseases are major global health problems, with high prevalence and mortality. However, current treatment strategies for kidney diseases fail to achieve satisfactory efficacy. Mesenchymal stem cell (MSC)-based therapy has been a promising strategy for treating kidney diseases. Preclinical studies have proven their safety and effectiveness in treating acute kidney injury (AKI) and chronic kidney disease (CKD), but the outcomes of clinical trials have shown very limited clinical efficacy. A variety of innovative approaches have been proposed to enhance the therapeutic potential of MSCs, and hydrogels are attractive candidates. Hydrogels are three-dimensional (3D) networks formed by hydrophilic polymers of natural or synthetic origin with diverse physical and chemical properties. They have been widely applied in the field of drug delivery and regenerative medicine, including MSC-based therapy. Many studies have proven that hydrogels can improve the therapeutic efficacy of MSCs for kidney diseases, but there are still challenges limiting the widespread application of this method. In this review, we introduce the application of MSCs in kidney diseases and the factors that influence therapeutic efficiency and focus on the beneficial effects of hydrogels in MSC-based therapy for AKI and CKD.

Effects of Expanded Hemodialysis with Medium Cut-Off Membranes on Maintenance Hemodialysis Patients: A Review.

Kidney failure is associated with high morbidity and mortality. Hemodialysis, the most prevalent modality of renal replacement therapy, uses the principle of semipermeable membranes to remove solutes and water in the plasma of patients with kidney failure. With the evolution of hemodialysis technology over the last half century, the clearance of small water-soluble molecules in such patients is adequate. However, middle molecules uremic toxins are still retained in the plasma and cause cardiovascular events, anemia, and malnutrition, which significantly contribute to poor quality of life and high mortality in maintenance hemodialysis patients. A new class of membrane, defined as a medium cut-off (MCO) membrane, has emerged in recent years. Expanded hemodialysis with MCO membranes is now recognized as the artificial kidney model closest to natural kidney physiology. This review summarizes the unique morphological characteristics and internal filtration-backfiltration mechanism of MCO membranes, and describes their effects on removing uremic toxins, alleviating inflammation and cardiovascular risk, and improving quality of life in maintenance hemodialysis patients.