Thrombin Preconditioning Improves the Therapeutic Efficacy of Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage Induced Neonatal Rats.

Severe intraventricular hemorrhage (IVH) remains a major cause of high mortality and morbidity in extremely preterm infants. Mesenchymal stem cell (MSC) transplantation is a possible therapeutic option, and development of therapeutics with enhanced efficacy is necessary. This study investigated whether thrombin preconditioning improves the therapeutic efficacy of human Wharton's jelly-derived MSC transplantation for severe neonatal IVH, using a rat model. Severe neonatal IVH was induced by injecting 150 µL blood into each lateral ventricle on postnatal day (P) 4 in Sprague-Dawley rats. After 2 days (P6), naïve MSCs or thrombin-preconditioned MSCs (1 × 105/10 µL) were transplanted intraventricularly. After behavioral tests, brain tissues and cerebrospinal fluid of P35 rats were obtained for histological and biochemical analyses, respectively. Thrombin-preconditioned MSC transplantation significantly reduced IVH-induced ventricular dilatation on in vivo magnetic resonance imaging, which was coincident with attenuations of reactive gliosis, cell death, and the number of activated microglia and levels of inflammatory cytokines after IVH induction, compared to naïve MSC transplantation. In the behavioral tests, the sensorimotor and memory functions significantly improved after transplantation of thrombin-preconditioned MSCs, compared to naïve MSCs. Overall, thrombin preconditioning significantly improves the therapeutic potential and more effectively attenuates brain injury, including progressive ventricular dilatation, gliosis, cell death, inflammation, and neurobehavioral functional impairment, in newborn rats with induced severe IVH than does naïve MSC transplantation.

Alginate-based composite sponge containing silver nanoparticles synthesized in situ.

Silver-based biomaterials have been developed in a variety of bactericidal applications, especially for wound dressings. In this study, silver nanoparticles (AgNPs) were synthesized in a sodium alginate solution and then the composite sponge containing AgNPs was prepared from the nanocolloid solution. The alginate-stabilized AgNPs had the mean negative zeta potential of -52.5mV, suggesting that the surface charge prevents the nanoparticles from aggregating through electrostatic repulsion. The alginate-AgNPs composite sponge had a highly enhanced antimicrobial activity compared to the alginate sponge. In spite of excellent cytocompatibility of the alginate sponge, the viability of the cell treated with the alginate-AgNPs composite sponge extract decreased to 86% of the control. The amount of proinflammatory cytokines released from macrophages treated with the alginate-AgNPs composite sponge was reduced. For the preparation of AgNPs-embedded composites, alginate can be a potential candidate stabilizing AgNPs and providing synergistic antimicrobial and antiinflammatory activities with AgNPs.