Abstract:
Oligodendrocytes are a type of glial cells that produce a lipid-rich membrane called myelin. Myelin assembles into a sheath and lines neuronal axons in the brain and spinal cord to insulate them. This not only increases the speed and efficiency of nerve signal transduction but also protects the axons from damage and degradation, which could trigger neuronal cell death. Demyelination, which is caused by a loss of myelin and oligodendrocytes, is a prominent feature of many neurological conditions, including Multiple sclerosis (MS), spinal cord injuries (SCI), and leukodystrophies. Demyelination is followed by a time of remyelination mediated by the recruitment of endogenous oligodendrocyte precursor cells, their migration to the injury site, and differentiation into myelin-producing oligodendrocytes. Unfortunately, endogenous remyelination is not sufficient to overcome demyelination, which explains why there are to date no regenerative-based treatments for MS, SCI, or leukodystrophies. To better understand the role of oligodendrocytes and develop cell-based remyelination therapies, human oligodendrocytes have been derived from somatic cells using cell reprogramming. This review will detail the different cell reprogramming methods that have been developed to generate human oligodendrocytes and their applications to disease modeling and cell-based remyelination therapies. Recent developments in the field have seen the derivation of brain organoids from pluripotent stem cells, and protocols have been devised to incorporate oligodendrocytes within the organoids, which will also be reviewed.
摘要:
少突胶质细胞是一种神经胶质细胞,可产生一种称为髓鞘的富含脂质的膜。髓磷脂组装到鞘中,并在大脑和脊髓中排列神经元轴突以使它们绝缘。这不仅提高了神经信号转导的速度和效率,而且保护了轴突免受损伤和降解,这可能引发神经元细胞死亡。脱髓鞘,这是由髓磷脂和少突胶质细胞的损失引起的,是许多神经系统疾病的突出特征,包括多发性硬化症(MS),脊髓损伤(SCI),和脑白质营养不良.脱髓鞘后是由内源性少突胶质细胞前体细胞募集介导的髓鞘再生时间,他们迁移到受伤部位,分化为产生髓鞘的少突胶质细胞。不幸的是,内源性髓鞘再生不足以克服脱髓鞘,这解释了为什么到目前为止还没有基于再生的MS治疗方法,SCI或脑白质营养不良。为了更好地了解少突胶质细胞的作用并开发基于细胞的髓鞘再生疗法,人类少突胶质细胞已经使用细胞重编程从体细胞中获得。这篇综述将详细介绍已开发用于生成人类少突胶质细胞的不同细胞重编程方法及其在疾病建模和基于细胞的髓鞘再生治疗中的应用。该领域的最新进展已经看到了从多能干细胞中衍生出脑类器官,和方案已被设计为在类器官中掺入少突胶质细胞,这也将被审查。