Biomaterials have long been the focus of research and hydrogels are representatives thereof. Hydrogels have attracted much attention in the medical sciences, especially as a candidate drug-carrier. Mesenchymal stem cells (MSC) and MSC-derived secretome are a promising therapeutic method, owing to the intrinsic therapeutic properties thereof. The low cell retention and poor survival rate of MSCs make further research difficult, which is a problem that hydrogel encapsulation largely solved. In this review, safety and feasibility of hydrogel-encapsulated MSCs, the improvement of the survival, retention, and targeting, and the enhancement of their therapeutic effect by hydrogels were studied. The status of the hydrogel-encapsulated MSC secretome was also discussed.

Endothelial barrier dysfunction is central to the pathogenesis of sepsis-associated acute lung injury (ALI). Microtubule (MT) dynamics in vascular endothelium are crucial for the regulation of endothelial barrier function. Unfractionated heparin (UFH) possesses various biological activities, such as anti-inflammatory activity and endothelial barrier protection during sepsis. Here, we investigated the effects and underlying mechanisms of UFH on lipopolysaccharide (LPS)-induced endothelial barrier dysfunction. C57BL/6 J mice were randomized into vehicle, UFH, LPS and LPS + UFH groups. Intraperitoneal injection of 30 mg/kg LPS was used to induce sepsis. Mice in the LPS + UFH group received intravenous UFH 0.5 h prior to LPS injection. Human pulmonary microvascular endothelial cells (HPMECs) were cultured for analyzing the effects of UFH on LPS-induced and nocodazole-induced hyperpermeability, F-actin remodeling, and LPS-induced p38 MAPK activation. UFH pretreatment significantly attenuated LPS-induced pulmonary histopathological changes, and increased the lung W/D ratio and Evans blue accumulation in vivo. Both in vivo and in vitro studies showed that UFH pretreatment blocked the LPS-induced increase in guanine nucleotide exchange factor (GEF-H1) expression and myosin phosphatase target subunit 1 (MYPT1) phosphorylation, and microtubule (MT) disassembly in LPS-induced ALI mouse model and human pulmonary microvascular endothelial cells (HPMECs). These results suggested that UFH ameliorated LPS-induced endothelial barrier dysfunction by inhibiting MT disassembly and GEF-H1 expression. In addition, UFH attenuated LPS-induced hyperpermeability of HPMECs and F-actin remodeling. In vitro, UFH pretreatment inhibited LPS-induced increase in monomeric tubulin expression and decrease in tubulin polymerization and acetylation. Meanwhile, UFH ameliorates nocodazole-induced MTs disassembly and endothelial barrier dysfunction.Additionally, UFH decreased p38 phosphorylation and activation, which was similar to the effect of the p38 MAPK inhibitor, SB203580. UFH exert its protective effects on pulmonary microvascular endothelial barrier dysfunction via microtubule stabilization and is associated with the p38 MAPK pathway.

Early detection of disease progression associated with severe COVID-19, and access to proper medical care lowers fatality rates of severe cases. Currently, no studies had systematically examined th...

Since December 2019, the coronavirus (COVID-19) pandemic has imposed huge burdens to the whole world, seriously affecting global economic growth, and threatening people’s lives and health. At present, some therapeutic regimens are available for treatment of COVID-19 pneumonia, including antiviral therapy, immunity therapy, anticoagulant therapy, and others. Among them, injection of mesenchymal stem cells (MSCs) is currently a promising therapy. The preclinical studies and clinical trials using MSCs and small extracellular vesicles derived from MSCs (MSC-sEVs) in treating COVID-19 were summarized. Then, the molecular mechanism, feasibility, and safety of treating COVID-19 with MSCs and MSC-sEVs were also discussed.

Fibrosis, as a shared hallmark, is prevalent in a variety of chronic diseases. However, current pharmacological strategies for fibrosis are limited in clinical application and efficacy due to issues such as insufficient targeting capability, systemic toxicity, and low bioavailability. The advent of nanotechnology has ushered in an era of novel therapeutic strategies for fibrosis, revolutionizing the treatment landscape. This article systematically reviews the dual applications of nanomaterials in fibrosis treatment: first, as nanoparticle drug delivery systems (NDDS) to enhance targeting, control release, and improve drug bioavailability; second, as therapeutic agents directly alleviating the onset and progression of fibrosis. Furthermore, this article further discusses the applications of nanomaterials with diverse designs and compositions in fibrosis affecting different organs.