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Repurposed Drugs to Enhance the Therapeutic Potential of Oligodendrocyte Precursor Cells Derived from Adult Rat
J Pascual-Guerra1,2, M Torres-Rico2, B Marín-Rodríguez2
1Servicio de Neurobiología-Investigación, IRYCIS, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.
Abstract:
Failure in the proliferation, recruitment, mobilization, and/or differentiation of oligodendrocyte precursor cells (OPCs) impedes remyelination in central nervous system (CNS) demyelinating diseases. Our group has recently achieved the generation of functional oligodendroglia through direct lineage conversion by expressing Sox10, Olig2, and Zfp536 genes in adult rat adipose tissue-derived stromal cells. The present study aimed to determine whether various repurposed drugs or molecules could enhance the myelinating capacities of these induced OPCs (iOPCs). We report that kainate, benztropine, miconazole, clobetasol, and baclofen promote in vitro iOPCs migration, differentiation, and ensheathing abilities through mechanisms similar to those observed in rat neural stem cell-derived OPCs. This research supports the potential use of iOPCs as they provide an alternative and reliable cell source for testing the effects of in vitro promyelinating repurposed drugs and for assessing the molecular and cellular mechanisms involved in therapeutic strategies for demyelinating diseases.
Insights
Repurposed drugs like kainate and benztropine enhance the myelinating abilities of lab-generated oligodendrocyte precursor cells (OPCs). This finding offers a new cell source for studying remyelination and testing therapies for central nervous system demyelinating diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Regenerative Medicine
Background:
- Demyelinating diseases, such as multiple sclerosis, are characterized by impaired remyelination due to oligodendrocyte precursor cell (OPC) dysfunction.
- Direct lineage conversion offers a potential method to generate functional OPCs for therapeutic applications.
- Identifying molecules that enhance OPC function is crucial for developing effective remyelination strategies.
Purpose of the Study:
- To investigate the potential of repurposed drugs to enhance the myelinating capacity of induced OPCs (iOPCs).
- To assess the in vitro effects of specific drugs on iOPC migration, differentiation, and ensheathing abilities.
- To validate iOPCs as a reliable model for drug screening and mechanistic studies in demyelinating diseases.
Main Methods:
- Generation of iOPCs by expressing Sox10, Olig2, and Zfp536 in adult rat adipose tissue-derived stromal cells.
- In vitro screening of repurposed drugs for their effects on iOPC behavior.
- Assessment of iOPC migration, differentiation, and myelinating potential.
Main Results:
- Kainate, benztropine, miconazole, clobetasol, and baclofen were identified as promoting iOPC migration, differentiation, and ensheathing.
- The observed mechanisms of action were comparable to those in neural stem cell-derived OPCs.
- These drugs enhance the functional capacity of iOPCs for remyelination.
Conclusions:
- Induced OPCs represent a viable alternative cell source for studying remyelination.
- Repurposed drugs can enhance the therapeutic potential of iOPCs for demyelinating diseases.
- This approach facilitates in vitro testing of promyelinating drugs and elucidation of underlying mechanisms.
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