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Exosomes from Human Dental Pulp Stem Cells Suppress Carrageenan-Induced Acute Inflammation in Mice

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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 × 106 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.

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ACKNOWLEDGEMENTS

This research was funded by the European Social Fund under the Global Grant measure (No. VP1-3.1-ŠMM-07-K-03-016).

Compliance with Ethical Standards

Human material was collected under the approval of the Lithuanian Bioethics Committee.

All procedures with animals were carried out in accordance with the guidelines of the European Union and were approved by the Lithuanian Ethics Committee on the use of the laboratory animals under State Veterinary Service.

Conflicts of Interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Stem Cell Biology, State Research Institute Centre for Innovative Medicine, Žygimantų 9, LT-01102, Vilnius, Lithuania

    Ugnė Pivoraitė, Akvilė Jarmalavičiūtė, Virginijus Tunaitis, Giedrė Ramanauskaitė, Aida Vaitkuvienė, Vytautas Kašėta, Genė Biziulevičienė, Algirdas Venalis & Augustas Pivoriūnas

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  1. Ugnė Pivoraitė
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  2. Akvilė Jarmalavičiūtė
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  4. Giedrė Ramanauskaitė
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  5. Aida Vaitkuvienė
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  9. Augustas Pivoriūnas
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Correspondence to Augustas Pivoriūnas.

ELECTRONIC SUPPLEMENTARY MATERIAL

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Supplemental table 1

Immunophenotypic characterization of SHEDs. SHEDs grown under serum-free medium MSC NutriStem XF medium (Biological Industries) were characterized by FACS for the expression of negative (CD45, CD34) and positive (CD90, CD73, CD105 and CD146) markers of MSC-like cells. (JPEG 260 kb) (PDF 75 kb)

Supplemental figure 1

Vesicle size distribution in exosomal preparations. Particle size range was estimated in PBS using a dynamic light scattering device (Brookhaven Instruments Corp., NY, USA). Measurements were performed in triplicate at a temperature of 25 °C (PDF 75 kb) (JPEG 260 kb)

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Pivoraitė, U., Jarmalavičiūtė, A., Tunaitis, V. et al. Exosomes from Human Dental Pulp Stem Cells Suppress Carrageenan-Induced Acute Inflammation in Mice. Inflammation 38, 1933–1941 (2015). https://doi.org/10.1007/s10753-015-0173-6

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  • DOI: https://doi.org/10.1007/s10753-015-0173-6

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