Placenta Stem/Stromal Cell-Derived Extracellular Vesicles for Potential Use in Lung Repair.

Many acute and chronic lung injuries are incurable and rank as the fourth leading cause of death globally. While stem cell treatment for lung injuries is a promising approach, there is growing evidence that the therapeutic efficacy of stem cells originates from secreted extracellular vesicles (EVs). Consequently, EVs are emerging as next-generation therapeutics. While EVs are extensively researched for diagnostic applications, their therapeutic potential to promote tissue repair is not fully elucidated. By housing and delivering tissue-repairing cargo, EVs refine the cellular microenvironment, modulate inflammation, and ultimately repair injury. Here, the potential use of EVs derived from two placental mesenchymal stem/stromal cell (MSC) lines is presented; a chorionic MSC line (CMSC29) and a decidual MSC cell line (DMSC23) for applications in lung diseases. Functional analyses using in vitro models of injury demonstrate that these EVs have a role in ameliorating injuries caused to lung cells. It is also shown that EVs promote repair of lung epithelial cells. This study is fundamental to advancing the field of EVs and to unlock the full potential of EVs in regenerative medicine.

Synthesis of Antimicrobial Gallium Nanoparticles Using the Hot Injection Method.

Antibiotic resistance continues to be an ongoing problem in global public health despite interventions to reduce antibiotic overuse. Furthermore, it threatens to undo the achievements and progress of modern medicine. To address these issues, the development of new alternative treatments is needed. Metallic nanoparticles have become an increasingly attractive alternative due to their unique physicochemical properties that allow for different applications and their various mechanisms of action. In this study, gallium nanoparticles (Ga NPs) were tested against several clinical strains of Pseudomonas aeruginosa (DFU53, 364077, and 365707) and multi-drug-resistant Acinetobacter baumannii (MRAB). The results showed that Ga NPs did not inhibit bacterial growth when tested against the bacterial strains using a broth microdilution assay, but they exhibited effects in biofilm production in P. aeruginosa DFU53. Furthermore, as captured by atomic force microscopy imaging, P. aeruginosa DFU53 and MRAB biofilms underwent morphological changes, appearing rough and irregular when they were treated with Ga NPs. Although Ga NPs did not affect planktonic bacterial growth, their effects on both biofilm formation and established biofilm demonstrate their potential role in the race to combat antibiotic resistance, especially in biofilm-related infections.

Quantum Dot Nanomedicine Formulations Dramatically Improve Pharmacological Properties and Alter Uptake Pathways of Metformin and Nicotinamide Mononucleotide in Aging Mice.

Orally administered Ag2S quantum dots (QDs) rapidly cross the small intestine and are taken up by the liver. Metformin and nicotinamide mononucleotide (NMN) target metabolic and aging processes within the liver. This study examined the pharmacology and toxicology of QD-based nanomedicines as carriers of metformin and NMN in young and old mice, determining if their therapeutic potency and reduced effects associated with aging could be improved. Pharmacokinetic studies demonstrated that QD-conjugated metformin and NMN have greater bioavailability, with selective accumulation in the liver following oral administration compared to unconjugated formulations. Pharmacodynamic data showed that the QD-conjugated medicines had increased physiological, metabolic, and cellular potency compared to unconjugated formulations (25× metformin; 100× NMN) and highlighted a shift in the peak induction of, and greater metabolic response to, glucose tolerance testing. Two weeks of treatment with low-dose QD-NMN (0.8 mg/kg/day) improved glucose tolerance tests in young (3 months) mice, whereas old (18 and 24 months) mice demonstrated improved fasting and fed insulin levels and insulin resistance. High-dose unconjugated NMN (80 mg/kg/day) demonstrated improvements in young mice but not in old mice. After 100 days of QD (320 µg/kg/day) treatment, there was no evidence of cellular necrosis, fibrosis, inflammation, or accumulation. Ag2S QD nanomedicines improved the pharmacokinetic and pharmacodynamic properties of metformin and NMN by increasing their therapeutic potency, bypassing classical cellular uptake pathways, and demonstrated efficacy when drug alone was ineffective in aging mice.

Isolation and Characterization of Extracellular Vesicles from Mesenchymal Stromal Cells.

Extracellular vesicles (EVs) have received immense attention in the past decade for their diverse use in diagnosis and therapeutics. Enhancing our understanding of EVs and increasing the reliability and reproducibility of EV research demands the use of standard isolation procedures and multiple characterization methods. Here we describe the most commonly used EV isolation method involving ultracentrifugation, and various characterization methods that include nanoparticle tracking analysis, atomic force microscopy and electron microscopy, which measure the size, concentration, and morphology of EVs.

Tropoelastin Implants That Accelerate Wound Repair.

A novel, pure, synthetic material is presented that promotes the repair of full-thickness skin wounds. The active component is tropoelastin and leverages its ability to promote new blood vessel formation and its cell recruiting properties to accelerate wound repair. Key to the technology is the use of a novel heat-based, stabilized form of human tropoelastin which allows for tunable resorption. This implantable material contributes a tailored insert that can be shaped to the wound bed, where it hydrates to form a conformable protein hydrogel. Significant benefits in the extent of wound healing, dermal repair, and regeneration of mature epithelium in healthy pigs are demonstrated. The implant is compatible with initial co-treatment with full- and split-thickness skin grafts. The implant's superiority to sterile bandaging, commercial hydrogel and dermal regeneration template products is shown. On this basis, a new concept for a prefabricated tissue repair material for point-of-care treatment of open wounds is provided.