Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis
Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis
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DOI：
10.3390/jcm9061681
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发表时间：
2020-06-01
影响因子：
3.9
通讯作者：
de Castro, Fernando
中科院分区：
文献类型：
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作者：
Bribian, Ana;Medina-Rodriguez, Eva M.;de Castro, Fernando
除了产生少突胶质细胞（生理条件下中枢神经系统（CNS）中唯一的髓鞘形成细胞）外，少突胶质细胞前体细胞（OPCs）还负责脱髓鞘病变后的自发髓鞘再生。它们存在于小鼠和人类的中枢神经系统中，无论是在发育过程中还是在成年期，但OPC的生理行为是如何在整个生命过程中被改变的尚不完全清楚。成人OPCs的活动仍然特别未被探索。值得注意的是，大多数参与opc介导的髓鞘再生的分子也参与了它们的发育，这一现象可能与临床相关。在本文中，我们比较了从新生、产后和成年小鼠的大脑皮层中分离的OPCs以及从神经外科成人大脑皮层组织中恢复的OPCs的内在特性。通过首次使用1H高分辨率魔角旋转核磁共振（1H HR-MAS NMR）光谱分析完整的OPCs，我们发现这些细胞在成熟阶段表现出明显的行为，并且在功能上具有不同的代谢模式。此外，它们对成纤维细胞生长因子-2 （FGF-2）和缺氧蛋白-1（已知在发育过程中对OPC生物学有影响的两种分子，并且在多发性硬化症（MS）患者中过度表达）的反应与它们的发育阶段和物种功能有关。我们的数据显示，成人和小鼠OPCs的行为以一种非常动态的方式不同，这在测试药物和正确设计有效的药物和/或细胞治疗MS时应该非常相关。
Besides giving rise to oligodendrocytes (the only myelin-forming cell in the Central Nervous System (CNS) in physiological conditions), Oligodendrocyte Precursor Cells (OPCs) are responsible for spontaneous remyelination after a demyelinating lesion. They are present along the mouse and human CNS, both during development and in adulthood, yet how OPC physiological behavior is modified throughout life is not fully understood. The activity of adult human OPCs is still particularly unexplored. Significantly, most of the molecules involved in OPC-mediated remyelination are also involved in their development, a phenomenon that may be clinically relevant. In the present article, we have compared the intrinsic properties of OPCs isolated from the cerebral cortex of neonatal, postnatal and adult mice, as well as those recovered from neurosurgical adult human cerebral cortex tissue. By analyzing intact OPCs for the first time with 1H High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, we show that these cells behave distinctly and that they have different metabolic patterns in function for their stage of maturity. Moreover, their response to Fibroblast Growth Gactor-2 (FGF-2) and anosmin-1 (two molecules that have known effects on OPC biology during development and that are overexpressed in individuals with Multiple Sclerosis (MS)) differs in relation to their developmental stage and in the function of the species. Our data reveal that the behavior of adult human and mouse OPCs differs in a very dynamic way that should be very relevant when testing drugs and for the proper design of effective pharmacological and/or cell therapies for MS.