Protective effects of EVs/exosomes derived from permanently growing human MSC on primary murine ALS motor neurons.

Autor: Gschwendtberger T; Department of Neurology, Hannover Medical School, Hannover 30625, Germany; Center for Systems Neuroscience (ZSN), Hannover, Germany., Thau-Habermann N; Department of Neurology, Hannover Medical School, Hannover 30625, Germany., von der Ohe J; Biochemistry and Tumor Biology Lab, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover 30625, Germany., Luo T; Biochemistry and Tumor Biology Lab, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover 30625, Germany., Hass R; Biochemistry and Tumor Biology Lab, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover 30625, Germany. Electronic address: hass.ralf@mh-hannover.de., Petri S; Department of Neurology, Hannover Medical School, Hannover 30625, Germany; Center for Systems Neuroscience (ZSN), Hannover, Germany. Electronic address: petri.susanne@mh-hannover.de.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2023 Nov 01; Vol. 816, pp. 137493. Date of Electronic Publication: 2023 Sep 27.
DOI: 10.1016/j.neulet.2023.137493
Abstrakt: In recent years, the neuroprotective potential of mesenchymal stroma-/stem-like cells (MSC) as well as of MSC-derived extracellular vesicles (EVs) like exosomes has been intensively explored. This included preclinical evaluation regarding treatment of neurodegenerative disorders such as the fatal motor neuron disease amyotrophic Lateral Sclerosis (ALS). Several studies have reported that MSC-derived exosomes can stimulate tissue regeneration and reduce inflammation. MSC release EVs and trophic factors and thereby modify cell-to-cell communication. These cell-free products may protect degenerating motor neurons (MNs) and represent a potential therapeutic approach for ALS. In the present study we investigated the effects of exosomes derived from a permanently growing MSC line on both, wild type and ALS (SOD1 G93A transgenic) primary motor neurons. Following application in a normal and stressed environment we could demonstrate beneficial effects of MSC exosomes on neurite growth and morphology indicating the potential for further preclinical evaluation and clinical therapeutic development. Investigation of gene expression profiles detected transcripts of several antioxidant and anti-inflammatory genes in MSC exosomes. Characterization of their microRNA (miRNA) content revealed miRNAs capable of regulating antioxidant and anti-apoptotic pathways.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE