Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology (GAIHST), Gachon University, Incheon 21936, Korea.
Neuroscience Research Institute, Gachon University, Incheon 21565, Korea.
Int J Mol Sci. 2020 Oct 30;21(21):8129. doi: 10.3390/ijms21218129.
Parkinson's disease (PD) is the second most common neurodegenerative disease, which is clinically and pathologically characterized by motor dysfunction and the loss of dopaminergic neurons in the substantia nigra, respectively. PD treatment with stem cells has long been studied by researchers; however, no adequate treatment strategy has been established. The results of studies so far have suggested that stem cell transplantation can be an effective treatment for PD. However, PD is a progressively deteriorating neurodegenerative disease that requires long-term treatment, and this has been insufficiently studied. Thus, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASC) for repeated vein transplantation over long-term in an animal model of PD. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice, hASCs were administered on the tail vein six times at two-week intervals. After the last injection of hASCs, motor function significantly improved. The number of dopaminergic neurons present in the nigrostriatal pathway was recovered using hASC transplantation. Moreover, the administration of hASC restored altered dopamine transporter expression and increased neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), in the striatum. Overall, this study suggests that repeated intravenous transplantation of hASC may exert therapeutic effects on PD by restoring BDNF and GDNF expressions, protecting dopaminergic neurons, and maintaining the nigrostriatal pathway.
帕金森病（PD）是第二常见的神经退行性疾病，其在临床上和病理学上分别表现为运动功能障碍和黑质中多巴胺能神经元的丧失。研究人员长期以来一直在研究用干细胞治疗 PD，但尚未建立足够的治疗策略。到目前为止的研究结果表明，干细胞移植可以是治疗 PD 的有效方法。然而，PD 是一种进行性恶化的神经退行性疾病，需要长期治疗，这方面的研究还不够充分。因此，我们旨在研究人脂肪干细胞（hASC）在 PD 动物模型中进行多次静脉移植的长期治疗潜力。在 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的 PD 模型小鼠中，在两周的间隔内通过尾静脉六次给予 hASC。在最后一次注射 hASC 后，运动功能显著改善。通过 hASC 移植恢复了黑质纹状体通路中存在的多巴胺能神经元的数量。此外，hASC 的给药恢复了改变的多巴胺转运蛋白表达，并增加了神经营养因子，如脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）在纹状体中的表达。总体而言，这项研究表明，重复静脉内移植 hASC 可能通过恢复 BDNF 和 GDNF 的表达、保护多巴胺能神经元和维持黑质纹状体通路来对 PD 发挥治疗作用。
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