ORC ID , Zhiguo Chen PhD 1 ORC ID , Paul Lu PhD 3 ORC ID ">
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REVIEW
Year : 2022  |  Volume : 17  |  Issue : 8  |  Page : 1633-1639

Motor neuron replacement therapy for amyotrophic lateral sclerosis


1 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
2 iXCells Biotechnologies USA, Inc., San Diego, CA, USA; Amogene Biotech, Xiamen, Fujian Province, China
3 Veterans Administration San Diego Healthcare System, San Diego; Department of Neurosciences, University of California - San Diego, La Jolla, CA, USA

Correspondence Address:
Lingyan Zhang
iXCells Biotechnologies USA, Inc., San Diego, CA; Amogene Biotech, Xiamen, Fujian Province

Paul Lu
Veterans Administration San Diego Healthcare System, San Diego; Department of Neurosciences, University of California - San Diego, La Jolla, CA
USA
Zhiguo Chen
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
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Source of Support: This work was supported by the Stem Cell and Translation National Key Project (No. 2016YFA0101403, to ZC), the National Natural Science Foundation of China (Nos. 81973351, 81661130160, 81422014, 81561138004, all to ZC), the Beijing Municipal Natural Science Foundation (No. 5142005, to ZC), Beijing Talents Foundation (No. 2017000021223TD03, to ZC), the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-Year Plan (No. CIT & TCD20180333, to ZC), the Beijing Medical System High Level Talent Award (No. 2015-3-063, to ZC), Beijing Municipal Health Commission Fund (No. PXM2020_026283_000005), Beijing One Hundred, Thousand, and Ten Thousand Talents Fund (No. 2018A03, to ZC), and the Royal Society-Newton Advanced Fellowship (No. NA150482, to ZC), and the USA Veterans Administration (No. I01 RX002264-01A2, to PL), Conflict of Interest: None


DOI: 10.4103/1673-5374.332123

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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.


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