論文 - 詳細
| RRC ID | 64061 |
|---|---|
| 著者 | Magota H, Sasaki M, Kataoka-Sasaki Y, Oka S, Ukai R, Kiyose R, Onodera R, Kocsis JD, Honmou O. |
| タイトル | Intravenous infusion of mesenchymal stem cells delays disease progression in the SOD1G93A transgenic amyotrophic lateral sclerosis rat model. |
| ジャーナル | Brain Res |
| Abstract |
ALS is a devastating neurodegenerative disease with few curative strategies. Both sporadic and familial ALS display common clinical features that show progressive paralysis. The pathogenesis remains unclear, but disruption of the blood-spinal cord barrier (BSCB) may contribute to the degeneration of motor neurons. Thus, restoration of the disrupted BSCB and neuroprotection for degenerating motor neurons could be therapeutic targets. We tested the hypothesis that an intravenous infusion of MSCs would delay disease progression through the preservation of BSCB function and increased expression of a neurotrophic factor, neurturin, in SOD1G93A ALS rats. When the open-field locomotor function was under 16 on the Basso, Beattie, and Bresnahan (BBB) scoring scale, the rats were randomized into two groups; one received an intravenous infusion of MSCs, while the other received vehicle alone. Locomotor function was recorded using BBB scoring and rotarod testing. Histological analyses, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), were performed. The MSC group exhibited reduced deterioration of locomotor activity compared to the vehicle group, which displayed progressive deterioration of hind limb function. We observed the protection of motor neuron loss and preservation of microvasculature using Evans blue leakage and immunohistochemical analyses in the MSC group. Confocal microscopy revealed infused green fluorescent protein+ (GFP+) MSCs in the spinal cord, and the GFP gene was detected by nested PCR. Neurturin expression levels were significantly higher in the MSC group. Thus, restoration of the BSCB and the protection of motor neurons might be contributing mechanisms to delay disease progression in SOD1G93A ALS rats. |
| 巻・号 | 1757 |
| ページ | 147296 |
| 公開日 | 2021-4-15 |
| DOI | 10.1016/j.brainres.2021.147296 |
| PII | S0006-8993(21)00021-4 |
| PMID | 33516815 |
| MeSH | Amyotrophic Lateral Sclerosis / genetics* Amyotrophic Lateral Sclerosis / therapy* Animals Disease Models, Animal Disease Progression Female Infusions, Intravenous / methods Locomotion / physiology Mesenchymal Stem Cells / cytology* Motor Neurons / cytology Nerve Degeneration / pathology* Neurodegenerative Diseases / metabolism Neurodegenerative Diseases / therapy Rats, Transgenic Spinal Cord / metabolism Superoxide Dismutase / genetics* |
| IF | 2.733 |
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オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ラット | W-Tg(CAG-GFP)184Ys (StrainID=525) |