Mouse Bone Marrow Mesenchymal Stem Cells Inhibit Sepsis-Induced Lung Injury in Mice via Exosomal SAA1

Sepsis is a global disease burden, and approximately 40% of cases develop acute lung injury (ALI). Bone marrow mesenchymal stromal cells (BMSCs) and their exosomes are widely used in treating a variety of diseases including sepsis. As an acute phase protein, serum amyloid A1 (SAA1) regulates inflammation and immunity. However, the role of SAA1 in BMSCs-exosomes in septic lung injury remains to be elucidated. Exosomes derived from serum and BMSCs were isolated by ultracentrifugation. SAA1 was silenced or overexpressed in mouse BMSCs using lentiviral plasmids, containing either SAA1-targeting short interfering RNAs or SAA1 cDNA. Sepsis was induced by cecal ligation and puncture (CLP). LPS was used to induce ALI in mice. Mouse alveolar macrophages were isolated by flow cytometry. Levels of SAA1, endotoxin, TNF-α, and IL-6 were measured using commercial kits. LPS internalization was monitored by immunostaining. RT-qPCR or immunoblots were performed to test gene and protein expressions. Serum exosomes of patients with sepsis-induced lung injury had significantly higher levels of SAA1, endotoxin, TNF-α, and IL-6. Overexpression of SAA1 in BMSCs inhibited CLP- or LPS-induced lung injury and decreased CLP- or LPS-induced endotoxin, TNF-α, and IL-6 levels. Administration of the SAA1 blocking peptide was found to partially inhibit SAA1-induced LPS internalization by mouse alveolar macrophages and reverse the protective effect of SAA1. In conclusion, BMSCs inhibit sepsis-induced lung injury through exosomal SAA1. These results highlight the importance of BMSCs, exosomes, and SAA1, which may provide novel directions for the treatment of septic lung injury

Mussel-Inspired One-Step Adherent Coating Rich in Amine Groups for Covalent Immobilization of Heparin: Hemocompatibility, Growth Behaviors of Vascular Cells, and Tissue Response

Heparin, an important polysaccharide, has been widely used for coatings of cardiovascular devices because of its multiple biological functions including anticoagulation and inhibition of intimal hyperplasia. In this study, surface heparinization of a commonly used 316L stainless steel (SS) was explored for preparation of a multifunctional vascular stent. Dip-coating of the stents in an aqueous solution of dopamine and hexamethylendiamine (HD) (PDAM/HD) was presented as a facile method to form an adhesive coating rich in primary amine groups, which was used for covalent heparin immobilization via active ester chemistry. A heparin grafting density of about 900 ng/cm² was achieved with this method. The retained bioactivity of the immobilized heparin was confirmed by a remarkable prolongation of the activated partial thromboplastin time (APTT) for about 15 s, suppression of platelet adhesion, and prevention of the denaturation of adsorbed fibrinogen. The Hep-PDAM/HD also presented a favorable microenvironment for selectively enhancing endothelial cell (EC) adhesion, proliferation, migration and release of nitric oxide (NO), and at the same time inhibiting smooth muscle cell (SMC) adhesion and proliferation. Upon subcutaneous implantation, the Hep-PDAM/HD exhibited mitigated tissue response, with thinner fibrous capsule and less granulation formation compared to the control 316L SS. This number of unique functions qualifies the heparinized coating as an attractive alternative for the design of a new generation of stents