Extracellular Microvesicles (MV's) Isolated from 5-Azacytidine-and-Resveratrol-Treated Cells Improve Viability and Ameliorate Endoplasmic Reticulum Stress in Metabolic Syndrome Derived Mesenchymal Stem Cells.

C Weiss, K Kornicka-Grabowska, M Mularczyk, N Siwinska, K Marycz
Author Information
  1. C Weiss: PferdePraxis Dr. Med. Vet. Daniel Weiss, Postmatte 14, CH-8807, Freienbach, Switzerland.
  2. K Kornicka-Grabowska: Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B street, A7 building, 50-375, Wroclaw, Poland.
  3. M Mularczyk: Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B street, A7 building, 50-375, Wroclaw, Poland.
  4. N Siwinska: Department of Internal Medicine and Clinic of Diseases of Horses, Dogs and Cats, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Pl. Grunwaldzki 47, 50-366, Wroclaw, Poland.
  5. K Marycz: Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B street, A7 building, 50-375, Wroclaw, Poland. krzysztofmarycz@interia.pl. ORCID

Abstract

Extracellular vesicles (EVs), a spherical membrane fragments including exosomes, are released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. As MVs cargo include DNA, RNA, miRNA, lipids and proteins their have gain special attention in the field of regenerative medicine. Depending on the type of transferred molecules, MVs may exert wide range of biological effects in recipient cells including pro-inflammatory and anti-apoptotic action. In presented paper, we isolated MVs form adipose derived mesenchymal stem cells (ASC) which underwent stimulation with 5-azacytydine and resveratrol (AZA/RES) in order to improve their therapeutic potential. Then, isolated MVs were applied to ASC with impaired cytophysiological properties, isolated from equine metabolic syndrome diagnosed animals. Using RT-PCR, immunofluorescence, ELISA, confocal microscopy and western blot, we have evaluated the effects of MVs on recipient cells. We have found, that MVs derived from AZA/RES treated ASC ameliorates apoptosis, senescence and endoplasmic reticulum (ER) stress in deteriorated cells, restoring their proper functions. The work indicates, that cells treated with AZA/RES through their paracrine action can rejuvenate recipient cells. However, further research needs to be performed in order to fully understand the molecular mechanisms of these bioactive factors action. Graphical Abstract Graphical abstract of presented study.

Keywords

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MeSH Term

Animals
Apoptosis
Autophagy
Azacitidine
Cell Survival
Cytokines
Endoplasmic Reticulum Stress
Extracellular Vesicles
Female
Horses
Inflammation
Male
Mesenchymal Stem Cells
Metabolic Syndrome
Oxidative Stress
Resveratrol

Chemicals

Cytokines
Azacitidine
Resveratrol

Word Cloud

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