Ren Hao, Wang Yuwei, Chen Yingying, Ma Feilong, Shi Qing, Wang Zichen, Gui Yaoting, Liu Jianbo, Tang Huiru
College of Chemistry and Chemical Engineering, Hunan University, Changsha, China.
Cheerland Watson Precision Medicine Ltd, Shenzhen, China.
IUBMB Life. 2025 Jan;77(1):e2936. doi: 10.1002/iub.2936.
Parkinson's disease (PD), characterized by progressive degeneration of dopaminergic neurons in substantia nigra, has no disease-modifying therapy. Mesenchymal stem cell (MSC) therapy has shown great promise as a disease-modifying solution for PD. Induced pluripotent stem cell-derived MSC (iMSC) not only has stronger neural repair function, but also helps solve the problem of MSC heterogeneity. So we evaluated the therapeutic effects of iMSCs on PD. iMSCs were administered by tail vein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD models of C57BL/6 mice. The results showed iMSCs increased body weights, inhibited the prolongation of latencies to descend in pole tests, the decrease of grip strength in grip strength tests and increase of open arm entries in elevated plus maze test, and showed a trend to alleviate striatal dopamine loss. They indicate iMSCs might improve functions partially by preserving striatal dopamine in PD. We for the first time (1) found that iMSC has therapeutic effects on PD; (2) tested specifically muscle strength in cell therapy for PD and found it increases muscle strength; (3) found cell therapy alleviated the increase of entries into the open arms in PD. It suggests iMSC is a promising candidate for clinical investigations and drug development for PD.
帕金森病(PD)以黑质中多巴胺能神经元的进行性变性为特征,目前尚无疾病修饰疗法。间充质干细胞(MSC)疗法作为一种针对PD的疾病修饰解决方案已显示出巨大潜力。诱导多能干细胞衍生的MSC(iMSC)不仅具有更强的神经修复功能,还有助于解决MSC异质性问题。因此,我们评估了iMSC对PD的治疗效果。在1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的C57BL/6小鼠PD模型中,通过尾静脉注射iMSC。结果显示,iMSC增加了体重,抑制了杆式试验中下降潜伏期的延长、握力试验中握力的降低以及高架十字迷宫试验中进入开放臂次数的增加,并呈现出减轻纹状体多巴胺损失的趋势。它们表明iMSC可能通过在PD中保留纹状体多巴胺来部分改善功能。我们首次(1)发现iMSC对PD具有治疗作用;(2)在PD细胞治疗中专门测试了肌肉力量,发现它能增加肌肉力量;(3)发现细胞治疗减轻了PD中进入开放臂次数的增加。这表明iMSC是PD临床研究和药物开发的一个有前景的候选者。