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用于增强成年大鼠脂肪组织来源的少突胶质前体细胞治疗潜力的药物再利用

Repurposed Drugs to Enhance the Therapeutic Potential of Oligodendrocyte Precursor Cells Derived from Adult Rat Adipose Tissue.

作者信息

Pascual-Guerra J, Torres-Rico M, Marín-Rodríguez B, Arasmou-Idrovo M S, García A G, Rodríguez-Navarro J A, Paíno C L

机构信息

Servicio de Neurobiología-Investigación, IRYCIS, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.

Fundación Teófilo Hernando, 28290 Madrid, Spain.

出版信息

Cells. 2025 Apr 2;14(7):533. doi: 10.3390/cells14070533.

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 , , and 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.

摘要

少突胶质前体细胞(OPCs)的增殖、募集、动员和/或分化失败会阻碍中枢神经系统(CNS)脱髓鞘疾病中的髓鞘再生。我们团队最近通过在成年大鼠脂肪组织来源的基质细胞中表达 、 和 基因,实现了通过直接谱系转化生成功能性少突胶质细胞。本研究旨在确定各种重新利用的药物或分子是否能增强这些诱导少突胶质前体细胞(iOPCs)的髓鞘形成能力。我们报告称,谷氨酸钾、苯海索、咪康唑、氯倍他索和巴氯芬通过与在大鼠神经干细胞来源的OPCs中观察到的机制相似的机制,促进体外iOPCs的迁移、分化和包裹能力。这项研究支持了iOPCs的潜在用途,因为它们为测试体外促髓鞘再生的重新利用药物的效果以及评估脱髓鞘疾病治疗策略中涉及的分子和细胞机制提供了一种替代且可靠的细胞来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccd8/11988185/f22c564ef52e/cells-14-00533-g001.jpg

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