title: Exosomes from Human Dental Pulp Stem Cells Suppress Carrageenan-Induced Acute Inflammation in Mice.
abstract: The primary goal of this study was to examine the effects of human dental pulp stem cell-derived exosomes on the carrageenan-induced acute inflammation in mice. Exosomes were purified by differential ultracentrifugation from the supernatants of stem cells derived from the dental pulp of human exfoliated deciduous teeth (SHEDs) cultivated in serum-free medium. At 1 h post-carrageenan injection, exosomes derived from supernatants of 2 × 10(6) SHEDs were administered by intraplantar injection to BALB/c mice; 30 mg/kg of prednisolone and phosphate-buffered saline (PBS) were used as positive and negative controls, respectively. Edema was measured at 6, 24, and 48 h after carrageenan injection. For the in vivo imaging experiments, AngioSPARK750, Cat B 750 FAST, and MMPSense 750 FAST were administered into the mouse tail vein 2 h post-carrageenan injection. Fluorescence images were acquired at 6, 24, and 48 h after edema induction by IVIS Spectrum in vivo imaging system. Exosomes significantly reduced the carrageenan-induced edema at all the time points studied (by 39.5, 41.6, and 25.6% at 6, 24, and 48 h after injection, respectively), to similar levels seen with the positive control (prednisolone). In vivo imaging experiments revealed that, both exosomes and prednisolone suppress activities of cathepsin B and matrix metalloproteinases (MMPs) at the site of carrageenan-induced acute inflammation, showing more prominent effects of prednisolone at the early stages, while exosomes exerted their suppressive effects gradually and at later time points. Our study demonstrates for the first time that exosomes derived from human dental pulp stem cells suppress carrageenan-induced acute inflammation in mice.
authors.affiliation: Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, Žygimantų 9, LT-01102, Vilnius, Lithuania.
authors.forename: Ugnė
authors.initials: U
authors.lastname: Pivoraitė
authors.forename: Akvilė
authors.initials: A
authors.lastname: Jarmalavičiūtė
authors.forename: Virginijus
authors.initials: V
authors.lastname: Tunaitis
authors.forename: Giedrė
authors.initials: G
authors.lastname: Ramanauskaitė
authors.forename: Aida
authors.initials: A
authors.lastname: Vaitkuvienė
authors.forename: Vytautas
authors.initials: V
authors.lastname: Kašėta
authors.forename: Genė
authors.initials: G
authors.lastname: Biziulevičienė
authors.forename: Algirdas
authors.initials: A
authors.lastname: Venalis
authors.forename: Augustas
authors.initials: A
authors.lastname: Pivoriūnas
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000633:toxicity*; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology* / Q000637:transplantation*; D004487:Edema / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D055354:Exosomes / Q000637:transplantation*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013234:Stem Cells
chemical_list: D002351:Carrageenan