内源性神经干细胞治疗多发性硬化的研究进展

Advances in Endogenous Neural Stem Cells-Based Therapeutics for Multiple Sclerosis

多发性硬化症(multiple sclerosis,MS)是一种以中枢神经系统(central nervous system,CNS)脱髓鞘病变为主要特点的自身免疫性疾病。髓鞘再生失败和轴突损害是MS患者遗留永久神经功能损害的病理基础,如何促进少突胶质细胞的再生以重建髓鞘的结构和功能并实现患者功能性恢复是迄今为止尚未解决的医学难题。在过去数十年中发现,具有自我更新和多向分化潜能的神经干细胞(neural stem cells,NSCs)在成年中枢神经系统中分布广泛,不仅参与神经组织稳态的维持,且能够响应脱髓鞘损伤而增殖、迁移至损伤区域分化产生髓鞘化少突胶质细胞(oligodendrocytes,OLs)以参与髓鞘再生修复。故激活诱导内源性神经干细胞分化并参与髓鞘再生,从而修复MS神经损伤并实现功能性恢复,同时避免了免疫排斥及一系列伦理道德问题,在治疗脱髓鞘疾病以及中枢神经系统损伤方面将会有广阔的临床应用前景。

Multiple sclerosis(MS)is a chronic,autoimmune,inflammatory,and demyelinating disorder in the central nervous system(CNS).Axonal degeneration and remyelination inefficiency are the major pathological basis for the permanent impairment of neurological function in patients with MS,which turns into a serious medical problem due to the absence of efficient method to activate the oligodendrocytes generation and myelination for enhancing the functional recovery in MS.The endogenous neural stem cells(NSCs)resident in the CNS are self-renewing and multipotent stem cells and play critical roles in neurogenesis and remyelination during homeostasis and injury repair.These endogenous NSCs were shown to have the capacity to generate oligodendrocytes(OLs)which were found to extensively contribute to remyelination in response to the demyelination damage.However,previous researches showed that these endogenous NSCs could not contribute to the significant functional recovery without the supportive microenvironment around the injury areas.Further understanding of the characterization and the potentials of these endogenous NSCs and their regulatory mechanisms will better the injury microenvironment in MS patients to induce the differentiation of the endogenous NSCs into oligodendrocytes and then the efficient migration and remyelination even in chronic demyelination stage.Together,numerous evidences hold the promise that the therapeutic strategy by activating endogenous NSCs would be a novel therapeutic approach to cure the MS patients,compared to the strategy by using exogenous stem cell transplantation,which could avoid the ethical and moral considerations.