| 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
|
| リソース情報 |
| ラット |
W-Tg(CAG-GFP)184Ys (StrainID=525) |
