Mitrečić Laura Dina, Park Eliana Eunjoo, El-Hajj Aya, Mitrečić Dinko
Laboratory for Stem Cells, Department of Regenerative Neuroscience, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, HR-10000 Zagreb, Croatia.
School of Medicine, University of Pavia, I-27100, Pavia, Italy.
Med Int (Lond). 2025 Jul 16;5(5):53. doi: 10.3892/mi.2025.252. eCollection 2025 Sep-Oct.
The present study investigated the effects of temperature modulation on neural precursors at various developmental stages. A well-proven neural stem cell model was employed and cells were exposed to hypothermia (32, 30 and 28˚C) and hyperthermia (39˚C) for periods of time. While deviations from the physiological temperature (37˚C) affected cell survival and generally reduced cell numbers, a distinct response was observed in late-stage precursors (day 14). Mild hypothermia (32˚C) at this stage preserved cell viability and increased the expression of Nestin, a marker of immature neuronal cells, while decreasing expression of the Map2, a marker of mature neurons. These combined findings suggest a potential dedifferentiation process and an enhanced regenerative capacity. Additionally, the levels of genes associated with cell adhesion, migration and differentiation (Ncam1 and Itgb1) were upregulated by mild hypothermia at day 14. On the whole, these findings highlight the differential response of neural precursors to temperature and suggest that hypothermia timing may be crucial for optimizing therapeutic strategies in neonatal brain injury.
本研究调查了温度调节对不同发育阶段神经前体细胞的影响。采用了一个经过充分验证的神经干细胞模型，将细胞暴露于低温（32、30和28˚C）和高温（39˚C）环境中一段时间。虽然偏离生理温度（37˚C）会影响细胞存活并普遍减少细胞数量，但在晚期前体细胞（第14天）中观察到了明显的反应。此阶段的轻度低温（32˚C）可保持细胞活力，并增加未成熟神经元细胞标志物巢蛋白（Nestin）的表达，同时降低成熟神经元标志物微管相关蛋白2（Map2）的表达。这些综合发现表明存在潜在的去分化过程和增强的再生能力。此外，在第14天，与细胞黏附、迁移和分化相关的基因（Ncam1和Itgb1）水平因轻度低温而上调。总体而言，这些发现突出了神经前体细胞对温度的不同反应，并表明低温处理的时机对于优化新生儿脑损伤的治疗策略可能至关重要。
