Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative fatal disorder in which motor neurons within the brain and spinal cord degenerate. A single infusion of mesenchymal stem cells (MSCs) delays disease progression by protecting motor neurons and restoring the blood-spinal cord barrier...

Full description

Bibliographic Details
Main Authors: Hirotoshi Magota, Masanori Sasaki, Yuko Kataoka-Sasaki, Shinichi Oka, Ryo Ukai, Ryo Kiyose, Rie Onodera, Jeffery D. Kocsis, Osamu Honmou
Format: Article
Language:English
Published: BMC 2021-05-01
Series:Molecular Brain
Subjects:
Online Access:https://doi.org/10.1186/s13041-021-00787-6
id doaj-d27beaaedafa4575b1fa10bc19ba9cc9
record_format Article
spelling doaj-d27beaaedafa4575b1fa10bc19ba9cc92021-05-09T11:26:15ZengBMCMolecular Brain1756-66062021-05-011411410.1186/s13041-021-00787-6Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosisHirotoshi Magota0Masanori Sasaki1Yuko Kataoka-Sasaki2Shinichi Oka3Ryo Ukai4Ryo Kiyose5Rie Onodera6Jeffery D. Kocsis7Osamu Honmou8Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of MedicineDepartment of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of MedicineDepartment of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of MedicineDepartment of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of MedicineDepartment of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of MedicineDepartment of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of MedicineDepartment of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of MedicineDepartment of Neurology, Yale University School of MedicineDepartment of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of MedicineAbstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative fatal disorder in which motor neurons within the brain and spinal cord degenerate. A single infusion of mesenchymal stem cells (MSCs) delays disease progression by protecting motor neurons and restoring the blood-spinal cord barrier in the SOD1G93A transgenic ALS rat model. However, the therapeutic effect of a single infusion of MSCs is transient and does not block disease progression. In this study, we demonstrated that repeated administration of MSCs (weekly, four times) increased the survival period, protected motor functions, and reduced deterioration of locomotor activity compared to a single infusion and vehicle infusion, after which rats displayed progressive deterioration of hind limb function. We also compared the days until gait ability was lost in rats and found that the repeated-infused group maintained gait ability compared to the single-infusion and vehicle-infusion groups. These results suggest that repeated administration of MSCs may prevent the deterioration of motor function and extend the lifespan in ALS.https://doi.org/10.1186/s13041-021-00787-6Amyotrophic lateral sclerosisMesenchymal stem cells intravenousMultiple dosesQuality of life
collection DOAJ
language English
format Article
sources DOAJ
author Hirotoshi Magota
Masanori Sasaki
Yuko Kataoka-Sasaki
Shinichi Oka
Ryo Ukai
Ryo Kiyose
Rie Onodera
Jeffery D. Kocsis
Osamu Honmou
spellingShingle Hirotoshi Magota
Masanori Sasaki
Yuko Kataoka-Sasaki
Shinichi Oka
Ryo Ukai
Ryo Kiyose
Rie Onodera
Jeffery D. Kocsis
Osamu Honmou
Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis
Molecular Brain
Amyotrophic lateral sclerosis
Mesenchymal stem cells intravenous
Multiple doses
Quality of life
author_facet Hirotoshi Magota
Masanori Sasaki
Yuko Kataoka-Sasaki
Shinichi Oka
Ryo Ukai
Ryo Kiyose
Rie Onodera
Jeffery D. Kocsis
Osamu Honmou
author_sort Hirotoshi Magota
title Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis
title_short Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis
title_full Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis
title_fullStr Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis
title_full_unstemmed Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis
title_sort repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the sod1g93a rat model of amyotrophic lateral sclerosis
publisher BMC
series Molecular Brain
issn 1756-6606
publishDate 2021-05-01
description Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative fatal disorder in which motor neurons within the brain and spinal cord degenerate. A single infusion of mesenchymal stem cells (MSCs) delays disease progression by protecting motor neurons and restoring the blood-spinal cord barrier in the SOD1G93A transgenic ALS rat model. However, the therapeutic effect of a single infusion of MSCs is transient and does not block disease progression. In this study, we demonstrated that repeated administration of MSCs (weekly, four times) increased the survival period, protected motor functions, and reduced deterioration of locomotor activity compared to a single infusion and vehicle infusion, after which rats displayed progressive deterioration of hind limb function. We also compared the days until gait ability was lost in rats and found that the repeated-infused group maintained gait ability compared to the single-infusion and vehicle-infusion groups. These results suggest that repeated administration of MSCs may prevent the deterioration of motor function and extend the lifespan in ALS.
topic Amyotrophic lateral sclerosis
Mesenchymal stem cells intravenous
Multiple doses
Quality of life
url https://doi.org/10.1186/s13041-021-00787-6
work_keys_str_mv AT hirotoshimagota repeatedinfusionofmesenchymalstemcellsmaintaintheconditiontoinhibitdeterioratedmotorfunctionleadingtoanextendedlifespaninthesod1g93aratmodelofamyotrophiclateralsclerosis
AT masanorisasaki repeatedinfusionofmesenchymalstemcellsmaintaintheconditiontoinhibitdeterioratedmotorfunctionleadingtoanextendedlifespaninthesod1g93aratmodelofamyotrophiclateralsclerosis
AT yukokataokasasaki repeatedinfusionofmesenchymalstemcellsmaintaintheconditiontoinhibitdeterioratedmotorfunctionleadingtoanextendedlifespaninthesod1g93aratmodelofamyotrophiclateralsclerosis
AT shinichioka repeatedinfusionofmesenchymalstemcellsmaintaintheconditiontoinhibitdeterioratedmotorfunctionleadingtoanextendedlifespaninthesod1g93aratmodelofamyotrophiclateralsclerosis
AT ryoukai repeatedinfusionofmesenchymalstemcellsmaintaintheconditiontoinhibitdeterioratedmotorfunctionleadingtoanextendedlifespaninthesod1g93aratmodelofamyotrophiclateralsclerosis
AT ryokiyose repeatedinfusionofmesenchymalstemcellsmaintaintheconditiontoinhibitdeterioratedmotorfunctionleadingtoanextendedlifespaninthesod1g93aratmodelofamyotrophiclateralsclerosis
AT rieonodera repeatedinfusionofmesenchymalstemcellsmaintaintheconditiontoinhibitdeterioratedmotorfunctionleadingtoanextendedlifespaninthesod1g93aratmodelofamyotrophiclateralsclerosis
AT jefferydkocsis repeatedinfusionofmesenchymalstemcellsmaintaintheconditiontoinhibitdeterioratedmotorfunctionleadingtoanextendedlifespaninthesod1g93aratmodelofamyotrophiclateralsclerosis
AT osamuhonmou repeatedinfusionofmesenchymalstemcellsmaintaintheconditiontoinhibitdeterioratedmotorfunctionleadingtoanextendedlifespaninthesod1g93aratmodelofamyotrophiclateralsclerosis
_version_ 1721454424946114560