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Updated: Nov 11, 2025
Generation of Oligodendrocytes and Oligodendrocyte-Conditioned Medium for Co-Culture Experiments
Published on: February 9, 2020
Overcoming the inhibitory microenvironment surrounding oligodendrocyte progenitor cells following experimental
Darpan Saraswat1, Hani J Shayya1, Jessie J Polanco2
1Department of Pharmacology and Toxicology, Jacob's School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
Abstract:
Chronic demyelination in the human CNS is characterized by an inhibitory microenvironment that impairs recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) leading to failed remyelination and axonal atrophy. By network-based transcriptomics, we identified sulfatase 2 (Sulf2) mRNA in activated human primary OPCs. Sulf2, an extracellular endosulfatase, modulates the signaling microenvironment by editing the pattern of sulfation on heparan sulfate proteoglycans. We found that Sulf2 was increased in demyelinating lesions in multiple sclerosis and was actively secreted by human OPCs. In experimental demyelination, elevated OPC Sulf1/2 expression directly impaired progenitor recruitment and subsequent generation of oligodendrocytes thereby limiting remyelination. Sulf1/2 potentiates the inhibitory microenvironment by promoting BMP and WNT signaling in OPCs. Importantly, pharmacological sulfatase inhibition using PI-88 accelerated oligodendrocyte recruitment and remyelination by blocking OPC-expressed sulfatases. Our findings define an important inhibitory role of Sulf1/2 and highlight the potential for modulation of the heparanome in the treatment of chronic demyelinating disease.
Insights
Sulfatase 1/2 (Sulf1/2) impairs remyelination in chronic demyelination by promoting inhibitory signaling in oligodendrocyte progenitor cells (OPCs). Blocking Sulf1/2 accelerates remyelination, offering a potential therapeutic strategy.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Chronic demyelination in the central nervous system (CNS) creates an inhibitory microenvironment that hinders oligodendrocyte progenitor cell (OPC) recruitment and differentiation, leading to failed remyelination and axonal damage.
- Heparan sulfate proteoglycans (HSPGs) play a critical role in modulating cellular signaling microenvironments, influencing cell behavior and tissue repair.
Purpose of the Study:
- To investigate the role of sulfatase 2 (Sulf2) in the inhibitory microenvironment of chronic demyelination.
- To explore the potential of targeting sulfatases for therapeutic intervention in demyelinating diseases.
Main Methods:
- Network-based transcriptomics to identify Sulf2 mRNA in human OPCs.
- Analysis of Sulf2 expression in human demyelinating lesions and OPCs.
- Experimental demyelination models to assess the impact of Sulf1/2 inhibition on remyelination.
- Pharmacological inhibition of sulfatases using PI-88.
Main Results:
- Sulfatase 2 (Sulf2) mRNA was identified in activated human primary OPCs and Sulf2 was elevated in demyelinating lesions of multiple sclerosis patients.
- Elevated Sulf1/2 expression in OPCs during experimental demyelination impaired oligodendrocyte generation and limited remyelination by potentiating BMP and WNT signaling.
- Pharmacological inhibition of sulfatases with PI-88 accelerated oligodendrocyte recruitment and enhanced remyelination.
Conclusions:
- Sulfatase 1/2 (Sulf1/2) plays a significant inhibitory role in chronic demyelinating diseases by hindering remyelination.
- Targeting the heparanome through sulfatase inhibition presents a promising therapeutic avenue for treating chronic demyelinating conditions.
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