Dimethylsulfoxide Inhibits Oligodendrocyte Fate Choice of Adult Neural Stem and Progenitor Cells

Abstract

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 toward 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.

Modulation of Neuronal Cell Affinity on PEDOT–PSS Nonwoven Silk Scaffolds for Neural Tissue Engineering

“…The lower cellular proliferation observed for the high coating concentration may have been due to reduced interfiber porosity (Figure A), which could have affected initial cell attachment. The presence of DMSO, even in very low concentrations, is known to inhibit neuronal cell activity. − The fact that the cellular response was not impaired on the DMSO-treated PEDOT–PSS functionalized scaffolds but rather enhanced over their PEDOT–PSS counterparts confirms that it is unlikely that there is any residual DMSO remaining and leaching into the culture after the preparation steps for the cell culture. The cellular response of these scaffolds could be further controlled by grafting multiple combinations of different ECM components such as laminin or peptide sequences known to direct neuronal cell behavior (e.g., IKVAV or GYIGSR) .…”

Effect of Escitalopram on the Number of DCX-Positive Cells and NMUR2 Receptor Expression in the Rat Hippocampus under the Condition of NPSR Receptor Blockade

“…DMSO was also considered a proapoptotic agent that distinctly stimulate cell death in an in vitro rat hippocampal culture preparation [ 60 ]. On the other hand, low concentrations (1%) of DMSO reduced oligodedrogenesis but stimulate astrogenesis in neural stem and progenitor cells cultures (NSPC) from the adult hippocampus [ 61 ]. Noteworthy, even very low concentrations (0.05%) of DMSO decreased the input resistance of hippocampal neurons with concomitantly reduced excitability [ 62 ].…”

Spontaneous remyelination following dimethyl sulfoxide-induced demyelination is accompanied by behavioral and neurological alteration in mice

“…Neurotoxicity of DMSO can be explained by its influence on neuronal myelin sheath. According to modern data acquired from in vitro experiments, DMSO is able to change the structure of myelin, decreasing synthesis of its main components and inhibiting oligodendrocyte genesis (O'Sullivan et al 2019;Sutrina et al 1987). At the same time there is no data about DMSO influence on structure of myelin sheath after systematical prolonged administration.…”