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Front. Neurosci. | doi: 10.3389/fnins.2019.01242

Dimethylsulfoxide inhibits oligodendrocyte fate choice of adult neural stem and progenitor cells

 Anna O'Sullivan1, 2, 3, Simona Lange2, 4, Peter Rotheneichner1, 2,  Ludwig Aigner2, 4, 5,  Francisco J. Rivera2, 4, 6, 7 and  Sebastien Couillard-Despres1, 2, 5*
  • 1Institute of Experimental Neuroregeneration, Paracelsus Medical University, Austria
  • 2Spinal Cord Injury and Tissue Regeneration Center Salzburg, Austria
  • 3Department of Otorhinolaryngology, Paracelsus Medical University, Austria
  • 4Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Austria
  • 5Austrian Cluster for Tissue Regeneration, Austria
  • 6Laboratory of Stem Cells and Neuroregeneration, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Austral University of Chile, Chile
  • 7Center for Interdisciplinary Studies on the Nervous System, Faculty of Medicine, Austral University of Chile, Chile

Several clinical trials address demyelinating diseases via transplantation of mesenchymal stromal cells (MSCs). Published reports detail that administration of MSCs in patients may provide a beneficial immunomodulation, and that factors secreted by MSCs are potent inducers of oligodendrogenesis.
Dimethylsulfoxide (DMSO) is widely used in life science and medicine as solvent, vehicle or cryoprotectant for cells used in transplantation. Importantly, most transplantation protocols do not include the removal of DMSO before injecting the cell suspension into patients. This indifferent application of DMSO is coming under increasing scrutiny following reports investigating its potential toxic side-effects. While the impact of DMSO on the central nervous system (CNS) has been partially studied, its effect on oligodendrocytes and oligodendrogenesis has not been addressed yet.
Consequently, we evaluated the influence of DMSO on oligodendrogenesis, and on the pro-oligodendrogenic effect of MSCs' secreted factors, using adult rat neural stem and progenitor cells (NSPCs). Here, we demonstrate that a concentration of 1 % DMSO robustly suppressed oligodendrogenesis and drove the fate of differentiating NSPCs towards astrogenesis. Furthermore, the pro-oligodendrogenic effect of MSC-conditioned medium (MSCCM) was also nearly completely abolished by the presence of 1 % DMSO. In this condition, inhibition of the Erk1/2 signal transduction pathway and high levels of Id2 expression, a specific inhibitor of oligodendrogenic differentiation, were detected. Furthermore, inflammatory demyelinating diseases may even potentiate the impact of DMSO on oligodendrogenesis.
Our results demonstrate the imperative of considering the strong anti-oligodendrogenic activity of DMSO when designing future clinical trial protocols.

Keywords: oligodendrogenesis, Neural stem cells (NSCs), Myelination and remyelination, DMSO (Dimethyl sulphoxide), Id2, olig2, astrocycte, Cell fate and differentiation

Received: 15 Jun 2019; Accepted: 04 Nov 2019.

Copyright: © 2019 O'Sullivan, Lange, Rotheneichner, Aigner, Rivera and Couillard-Despres. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Sebastien Couillard-Despres, Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Salzburg, Austria, s.couillard-despres@pmu.ac.at