The biology of CNS remyelination has attracted considerable interest in recent years because of its translational potential to yield regenerative therapies for the treatment of chronic and progressive demyelinating diseases such as multiple sclerosis (MS). Critical to devising myelin regenerative therapies is a detailed understanding of how remyelination occurs. The accepted dogma, based on animal studies, has been that the myelin sheaths of remyelination are made by oligodendrocytes newly generated from adult oligodendrocyte progenitor cells in a classical regenerative process of progenitor migration, proliferation and differentiation. However, recent human and a growing number of animal studies have revealed a second mode of remyelination in which mature oligodendrocytes surviving within an area of demyelination are able to regenerate new myelin sheaths. This discovery, while opening up new opportunities for therapeutic remyelination, has also raised the question of whether there are fundamental differences in myelin regeneration between humans and some of the species in which experimental remyelination studies are conducted. Here we review how this second mode of remyelination can be integrated into a wider and revised framework for understanding remyelination in which apparent species differences can be reconciled but that also raises important questions for future research.

近年来，中枢神经系统髓鞘再生的生物学引起了人们极大的兴趣，因为它具有转化潜力，可以产生再生疗法，用于治疗多发性硬化症（MS）等慢性和进行性脱髓鞘疾病。设计髓鞘再生疗法的关键是详细了解髓鞘再生如何发生。基于动物研究的公认教条是，髓鞘再生的髓鞘是由成体少突胶质祖细胞在祖细胞迁移、增殖和分化的经典再生过程中新生成的少突胶质细胞形成的。然而，最近的人类和越来越多的动物研究揭示了第二种髓鞘再生模式，其中脱髓鞘区域内存活的成熟少突胶质细胞能够再生新的髓鞘。这一发现虽然为治疗性髓鞘再生开辟了新的机会，但也提出了一个问题：人类与进行实验性髓鞘再生研究的一些物种之间的髓鞘再生是否存在根本差异。在这里，我们回顾了如何将第二种髓鞘再生模式整合到更广泛和修订的框架中，以了解髓鞘再生，在该框架中可以调和明显的物种差异，但这也为未来的研究提出了重要问题。