Department of Life Science and Graduate Institute of Biotechnology, 63373National Dong Hwa University, Hualien, Taiwan, R.O.C.
Taiwan Mitochondrion Applied Technology Co., Ltd., Hsinchu, Taiwan, R.O.C.
Cell Transplant. 2020 Jan-Dec;29:963689720960185. doi: 10.1177/0963689720960185.
Patients with multiple system atrophy (MSA), a progressive neurodegenerative disorder of adult onset, were found less than 9 years of life expectancy after onset. The disorders include bradykinesia and rigidity commonly seen in Parkinsonism disease and additional signs such as autonomic dysfunction, ataxia, or dementia. In clinical treatments, MSA poorly responds to levodopa, the drug used to remedy Parkinsonism disease. The exact cause of MSA is still unknown, and exploring a therapeutic solution to MSA remains critical. A transgenic mouse model was established to study the feasibility of human adipose-derived stem cell (ADSC) therapy in vivo. The human ADSCs were transplanted into the striatum of transgenic mice via intracerebral injection. As compared with sham control, we reported significantly enhanced rotarod performance of transgenic mice treated with ADSC at an effective dose, 2 × 10 ADSCs/mouse. Our ex vivo feasibility study supported that intracerebral transplantation of ADSC might alleviate striatal degeneration in MSA transgenic mouse model by improving the nigrostriatal pathway for dopamine, activating autophagy for α-synuclein clearance, decreasing inflammatory signal, and further cell apoptosis, improving myelination and cell survival at caudate-putamen.
多系统萎缩(MSA)患者的预期寿命不到发病后 9 年,这是一种成人起病的进行性神经退行性疾病。这些疾病包括帕金森病常见的运动迟缓与僵硬,以及自主神经功能障碍、共济失调或痴呆等其他症状。在临床治疗中,MSA 对左旋多巴(用于治疗帕金森病的药物)反应不佳。MSA 的确切病因仍不清楚,探索其治疗方法仍然至关重要。研究人员建立了一种转基因小鼠模型,以研究体内人类脂肪来源干细胞(ADSC)治疗的可行性。通过脑内注射将人 ADSC 移植到转基因小鼠纹状体中。与假手术对照相比,我们报道了有效剂量(每只小鼠 2×10 个 ADSC)的 ADSC 治疗可显著提高转基因小鼠的旋转棒性能。我们的体外可行性研究支持通过改善多巴胺的黑质纹状体通路、激活α-突触核蛋白清除的自噬、减少炎症信号和进一步的细胞凋亡、改善尾壳核的髓鞘形成和细胞存活,来减轻 MSA 转基因小鼠模型纹状体的退化。