Department of Neuroscience, University Medical Center Groningen, A.Deusinglaan 1, 9713AV, Groningen, The Netherlands.
Glia. 2015 Apr;63(4):513-30. doi: 10.1002/glia.22769. Epub 2014 Nov 24.
Studies on myelination and oligodendrocyte development are inevitably linked with demyelinating conditions such as multiple sclerosis (MS), leukodystrophies or spinal cord injury (SCI). Chronic loss of myelin, subsequently leading to neurodegeneration, is the ultimate cause of severe and permanent disability. Thus, fast restoration of myelin (remyelination) is essential for circumventing demyelination-caused pathologies. Implantation of exogenous remyelinating cells has been considered as a potential remyelination strategy. Researchers have examined a variety of cell types endowed with myelin-forming capacity (oligodendrocytes, Schwann cells, olfactory ensheathing cells etc.) in vitro and in vivo for their potential application as myelin restoring cell grafts. This review gives a summary of studies on the generation and testing of pure suspensions of human oligodendrocytes as a clinically relevant, efficient cellular tool for treating myelin pathology. We start with a brief overview of the current knowledge on the development of human oligodendrocytes from the late stages of embryogenesis up to the early postnatal stage. Insight in the specific extrinsic and intrinsic factors regulating normal oligodendrogenesis is crucial in order to achieve and maintain a sufficient population of engraftable functional oligodendrocytes in vitro. We discuss potential sources of human oligodendrocytes, including novel oligodendrocyte generation strategies employing induced pluripotent stem cells (iPSCs) and direct conversion technology. Finally, we provide a systematic overview of (the outcome of) experimental studies, in which human oligodendrocytes were tested for their (re)myelination capacity and efficiency.
髓鞘形成和少突胶质细胞发育的研究不可避免地与脱髓鞘疾病有关,如多发性硬化症(MS)、白质营养不良或脊髓损伤(SCI)。髓鞘的慢性丢失,随后导致神经退行性变,是严重和永久性残疾的最终原因。因此,快速恢复髓鞘(髓鞘再生)对于避免脱髓鞘引起的病变至关重要。植入外源性髓鞘再生细胞被认为是一种潜在的髓鞘再生策略。研究人员已经在体外和体内研究了多种具有髓鞘形成能力的细胞类型(少突胶质细胞、施万细胞、嗅鞘细胞等),以评估它们作为髓鞘修复细胞移植物的潜在应用。
这篇综述总结了关于人少突胶质细胞纯悬浮液的产生和测试的研究,作为一种临床相关的、有效的细胞工具,用于治疗髓鞘病理。我们首先简要概述了从胚胎发育晚期到出生后早期人类少突胶质细胞的发展的现有知识。了解调节正常少突胶质细胞发生的特定外在和内在因素对于实现和维持体外可移植功能少突胶质细胞的足够数量至关重要。
我们讨论了人少突胶质细胞的潜在来源,包括利用诱导多能干细胞(iPSCs)和直接转化技术产生新的少突胶质细胞的策略。最后,我们提供了一个系统的综述,其中包括对人少突胶质细胞的(再)髓鞘化能力和效率进行测试的实验研究的结果。