Human oligodendrocytes in remyelination research

Marcin Czepiel,Erik Boddeke,and Sjef Copray

Human oligodendrocytes in remyelination research

Marcin Czepiel,Erik Boddeke,and Sjef Copray

Department of Neuroscience,University Medical Center Groningen

摘自

《GLIA》2015,63:513-530.

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.

induced pluripotent stem cells;multiple sclerosis;neural stem cells;transplantation

（唐穎馨編譯）

人類少突膠質(zhì)細胞在髓鞘修復中的作用

有關髓鞘和少突膠質(zhì)細胞的研究大部分與脫髓鞘疾病相關，如多發(fā)性硬化、腦白質(zhì)營養(yǎng)不良或脊髓損傷。髓鞘慢性脫失，慢慢導致神經(jīng)退行性變，最終導致永久而嚴重的神經(jīng)功能喪失。因此，盡快恢復髓鞘是修復脫髓鞘疾病的最有效方法。移植外源性的髓鞘再生細胞是一個有希望的治療方法。已有多項在體和離體實驗將各種具有髓鞘形成功能細胞（少突膠質(zhì)細胞、施萬細胞、嗅鞘細胞等）進行移植，觀察其髓鞘修復功能。本綜述對將人類少突膠質(zhì)細胞用于治療脫髓鞘疾病的相關研究進行總結。首先，對人類少突膠質(zhì)細胞從胚胎發(fā)育晚期到產(chǎn)后早期的發(fā)育過程進行簡要的綜述。然后，對各種內(nèi)源性和外源性的少突膠質(zhì)細胞調(diào)節(jié)因子的研究進行總結。在離體實驗中，必須調(diào)控好各種調(diào)節(jié)因子才能使培養(yǎng)的少突膠質(zhì)細胞達到足夠的數(shù)量用于移植。之后，探討了人類少突膠質(zhì)細胞的可能來源，包括一些新型的少突膠質(zhì)細胞生產(chǎn)策略，如誘導多能干細胞誘導直接分化為少突膠質(zhì)細胞。最后，本綜述對人類少突膠質(zhì)細胞的髓鞘再生功能和效率進行了系統(tǒng)的回顧。

誘導多能干細胞；多發(fā)性硬化；神經(jīng)干細胞；移植

R741;R741.02;R741.05

ADOI10.3870/sjsscj.2015.02.014