Liu Bochao, Li Mo, Zhang Lingyan, Chen Zhiguo, Lu Paul
Cell Therapy Center, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, and Key Laboratory of Neurodegenerative Diseases, Ministry of Education; Center of Neural Injury and Repair; Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China.
iXCells Biotechnologies USA, Inc., San Diego, CA, USA; Amogene Biotech, Xiamen, Fujian Province, China.
Neural Regen Res. 2022 Aug;17(8):1633-1639. doi: 10.4103/1673-5374.332123.
Amyotrophic lateral sclerosis is a motor neuron degenerative disease that is also known as Lou Gehrig's disease in the United States, Charcot's disease in France, and motor neuron disease in the UK. The loss of motor neurons causes muscle wasting, paralysis, and eventually death, which is commonly related to respiratory failure, within 3-5 years after onset of the disease. Although there are a limited number of drugs approved for amyotrophic lateral sclerosis, they have had little success at treating the associated symptoms, and they cannot reverse the course of motor neuron degeneration. Thus, there is still a lack of effective treatment for this debilitating neurodegenerative disorder. Stem cell therapy for amyotrophic lateral sclerosis is a very attractive strategy for both basic and clinical researchers, particularly as transplanted stem cells and stem cell-derived neural progenitor/precursor cells can protect endogenous motor neurons and directly replace the lost or dying motor neurons. Stem cell therapies may also be able to re-establish the motor control of voluntary muscles. Here, we review the recent progress in the use of neural stem cells and neural progenitor cells for the treatment of amyotrophic lateral sclerosis. We focus on MN progenitor cells derived from fetal central nervous system tissue, embryonic stem cells, and induced pluripotent stem cells. In our recent studies, we found that transplanted human induced pluripotent stem cell-derived motor neuron progenitors survive well, differentiate into motor neurons, and extend axons into the host white matter, not only in the rostrocaudal direction, but also along motor axon tracts towards the ventral roots in the immunodeficient rat spinal cord. Furthermore, the significant motor axonal extension after neural progenitor cell transplantation in amyotrophic lateral sclerosis models demonstrates that motor neuron replacement therapy could be a promising therapeutic strategy for amyotrophic lateral sclerosis, particularly as a variety of stem cell derivatives, including induced pluripotent stem cells, are being considered for clinical trials for various diseases.
肌萎缩侧索硬化症是一种运动神经元退行性疾病，在美国也被称为卢伽雷氏病，在法国被称为夏科氏病，在英国被称为运动神经元病。运动神经元的丧失会导致肌肉萎缩、瘫痪，并最终导致死亡，这通常与疾病发作后3至5年内的呼吸衰竭有关。尽管批准用于肌萎缩侧索硬化症的药物数量有限，但它们在治疗相关症状方面收效甚微，且无法逆转运动神经元变性的进程。因此，对于这种使人衰弱的神经退行性疾病，仍然缺乏有效的治疗方法。肌萎缩侧索硬化症的干细胞疗法对基础研究人员和临床研究人员来说都是一个非常有吸引力的策略，特别是因为移植的干细胞和干细胞衍生的神经祖细胞/前体细胞可以保护内源性运动神经元，并直接替代丢失或即将死亡的运动神经元。干细胞疗法或许还能够重新建立对随意肌的运动控制。在此，我们综述了使用神经干细胞和神经祖细胞治疗肌萎缩侧索硬化症的最新进展。我们重点关注源自胎儿中枢神经系统组织、胚胎干细胞和诱导多能干细胞的运动神经元祖细胞。在我们最近的研究中，我们发现移植的人诱导多能干细胞衍生的运动神经元祖细胞存活良好，分化为运动神经元，并将轴突延伸至宿主白质，不仅在头尾方向，而且沿着运动轴突束向免疫缺陷大鼠脊髓的腹根延伸。此外，在肌萎缩侧索硬化症模型中神经祖细胞移植后显著的运动轴突延伸表明，运动神经元替代疗法可能是治疗肌萎缩侧索硬化症的一种有前景的治疗策略，特别是因为包括诱导多能干细胞在内的多种干细胞衍生物正在被考虑用于各种疾病的临床试验。
