Jeon Gye Sun, Im Wooseok, Shim Yu-Mi, Lee Mijung, Kim Myung-Jin, Hong Yoon-Ho, Seong Seung-Yong, Kim Manho, Sung Jung-Joon
Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
Neurochem Res. 2016 Apr;41(4):913-23. doi: 10.1007/s11064-015-1774-z. Epub 2015 Dec 8.
Amyotrophic lateral sclerosis (ALS) is a devastating human neurodegenerative disease. The precise pathogenic mechanisms of the disease remain uncertain, and as of yet, there is no effective cure. Human adipose stem cells (hASC) can be easily obtained during operative procedures. hASC have a clinically feasible potential to treat neurodegenerative disorders, since cytosolic extract of hASC contain a number of essential neurotrophic factors. In this study, we investigated effects of hASC extract on the SOD1 G93A mouse model of ALS and in vitro test. Administration of hASC extract improved motor function and prolonged the time until symptom onset, rotarod failure, and death in ALS mice. In the hASC extracts group, choline acetyltransferase immunostaining in the ventral horn of the lumbar spinal cord showed a large number of motor neurons, suggesting normal morphology. The neuroprotective effect of hASC extract in ALS mice was also suggested by western blot analysis of spinal cord extract from ALS mice and in vitro test. hASC extract treatment significantly increased expression of p-Akt, p-CREB, and PGC-1α in SOD1 G93A mouse model and in vitro test. Our results indicated that hASC extract reduced apoptotic cell death and recovered mutant SOD1-induced mitochondrial dysfunction. Moreover, hASC extract reduced mitochondrial membrane potential. In conclusion, we have demonstrated, for the first time, that hASC extract exert a potential therapeutic action in the SOD1 G93A mouse model of ALS and in vitro test. These findings suggest that hASC hold promise as a novel therapeutic strategy for treating ALS.
肌萎缩侧索硬化症（ALS）是一种毁灭性的人类神经退行性疾病。该疾病的确切致病机制仍不确定，截至目前，尚无有效的治疗方法。人脂肪干细胞（hASC）在手术过程中很容易获得。hASC具有临床上可行的治疗神经退行性疾病的潜力，因为hASC的胞质提取物含有多种必需的神经营养因子。在本研究中，我们研究了hASC提取物对ALS的SOD1 G93A小鼠模型的影响以及体外试验。给予hASC提取物可改善运动功能，并延长ALS小鼠出现症状、转棒试验失败和死亡的时间。在hASC提取物组中，腰脊髓腹角的胆碱乙酰转移酶免疫染色显示有大量运动神经元，提示形态正常。对ALS小鼠脊髓提取物的蛋白质印迹分析和体外试验也表明hASC提取物对ALS小鼠具有神经保护作用。hASC提取物治疗显著增加了SOD1 G93A小鼠模型和体外试验中p-Akt、p-CREB和PGC-1α的表达。我们的结果表明，hASC提取物减少了凋亡细胞死亡，并恢复了突变型SOD1诱导的线粒体功能障碍。此外，hASC提取物降低了线粒体膜电位。总之，我们首次证明hASC提取物在ALS的SOD1 G93A小鼠模型和体外试验中发挥了潜在的治疗作用。这些发现表明，hASC有望成为治疗ALS的一种新的治疗策略。
