Nishimura Hinata, Kerever Aurelien, Kato Kana, Ono Tatsuki, Nakayama Shiomi, Tanaka Takahiro, Abe Ryusei, Arikawa-Hirasawa Eri
Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Neurosci Lett. 2025 Jan 18;846:138079. doi: 10.1016/j.neulet.2024.138079. Epub 2024 Dec 9.
Loss of oligodendrocytes causes severe neurological damage. Oligodendrogenesis is the production of new oligodendrocytes throughout life and includes several developmental stages starting from oligodendrocyte precursor cells (OPCs). The GPR17-expressing cell population, an important intermediate stage in oligodendrocyte development, acts as a reservoir responding to brain injury and ischemia. GPR17 plays a complex role in oligodendrocyte maturation and response to injury; its activation promotes differentiation into more mature phenotypes. However, our understanding of GPR17-expressing oligodendrocytes in vitro remains limited. No methods have been elucidated for studying these short-lived and changeable cell populations using culture systems. The extracellular matrix (ECM) plays an important role in regulating the proliferation and differentiation of these cells; however, conventional two-dimensional culture systems cannot reproduce the complex structure and environmental conditions of the ECM in vivo. Herein, a culture system with decellularized brain tissue that retains organized ECM scaffolds was introduced to better mimic the in vivo environment. This system enabled the study of interactions between OPCs, ECM, and other cell types. Neurospheres containing progenitor cells that differentiate into oligodendrocyte lineage cells, neurons, and astrocytes were transplanted into decellularized brain slices. The results showed that this method not only promoted stem cell differentiation but also significantly enhanced differentiation into oligodendrocytes when supplemented with oligo buffer. This model system provides a better understanding of the interaction between OPCs and the ECM and a novel approach for studying the differentiation of GPR17-expressing cells, which may be useful for future therapeutic strategies for promoting remyelination and central nervous system repair.
少突胶质细胞的缺失会导致严重的神经损伤。少突胶质细胞生成是指在整个生命过程中产生新的少突胶质细胞，包括从少突胶质前体细胞（OPCs）开始的几个发育阶段。表达GPR17的细胞群体是少突胶质细胞发育的一个重要中间阶段，可作为应对脑损伤和缺血的储备库。GPR17在少突胶质细胞成熟和对损伤的反应中发挥着复杂的作用；其激活促进向更成熟表型的分化。然而，我们对体外表达GPR17的少突胶质细胞的了解仍然有限。尚未阐明使用培养系统研究这些寿命短且易变的细胞群体的方法。细胞外基质（ECM）在调节这些细胞的增殖和分化中起重要作用；然而，传统的二维培养系统无法再现体内ECM的复杂结构和环境条件。在此，引入了一种具有保留有组织的ECM支架的脱细胞脑组织的培养系统，以更好地模拟体内环境。该系统能够研究OPCs、ECM和其他细胞类型之间的相互作用。将含有可分化为少突胶质细胞谱系细胞、神经元和星形胶质细胞的祖细胞的神经球移植到脱细胞脑切片中。结果表明，该方法不仅促进了干细胞分化，而且在添加少突胶质细胞缓冲液时还显著增强了向少突胶质细胞的分化。该模型系统有助于更好地理解OPCs与ECM之间的相互作用，并为研究表达GPR17的细胞的分化提供了一种新方法，这可能对未来促进髓鞘再生和中枢神经系统修复的治疗策略有用。
