Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke.
Humans
Rats
Animals
Brain-Derived Neurotrophic Factor
/ metabolism
Ischemic Stroke
Vascular Endothelial Growth Factor A
/ metabolism
Bone Marrow
/ metabolism
Rats, Wistar
Brain Ischemia
/ metabolism
Stroke
/ therapy
Infarction, Middle Cerebral Artery
/ therapy
Mesenchymal Stem Cells
/ metabolism
RNA, Messenger
/ metabolism
Stromal Cells
/ metabolism
Cerebral ischemic infarct
Regenerative medicine
Rehabilitation
SB623
Voluntary exercise
Journal
Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581
Informations de publication
Date de publication:
24 Jan 2023
24 Jan 2023
Historique:
received:
11
06
2022
accepted:
09
01
2023
entrez:
23
1
2023
pubmed:
24
1
2023
medline:
26
1
2023
Statut:
epublish
Résumé
Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke. Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 × 10 SB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p < 0.05). The cerebral infarct area of SB623 + Ex group was significantly decreased compared to those in all other groups (p < 0.05). The number of BrdU/Doublecortin (Dcx) double-positive cells in the subventricular zone (SVZ) and the dentate gyrus (DG), the laminin-positive area in the ischemic boundary zone (IBZ), and the mRNA level of BDNF and VEGF in SB623 + Ex group were significantly increased compared to those in all other groups (p < 0.05). This study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous neurogenesis and angiogenesis after cerebral ischemia, possibly through a mechanism involving the up-regulation of BDNF and VEGF.
Sections du résumé
BACKGROUND
BACKGROUND
Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke.
METHODS
METHODS
Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 × 10
RESULTS
RESULTS
SB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p < 0.05). The cerebral infarct area of SB623 + Ex group was significantly decreased compared to those in all other groups (p < 0.05). The number of BrdU/Doublecortin (Dcx) double-positive cells in the subventricular zone (SVZ) and the dentate gyrus (DG), the laminin-positive area in the ischemic boundary zone (IBZ), and the mRNA level of BDNF and VEGF in SB623 + Ex group were significantly increased compared to those in all other groups (p < 0.05).
CONCLUSIONS
CONCLUSIONS
This study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous neurogenesis and angiogenesis after cerebral ischemia, possibly through a mechanism involving the up-regulation of BDNF and VEGF.
Identifiants
pubmed: 36691091
doi: 10.1186/s13287-023-03236-4
pii: 10.1186/s13287-023-03236-4
pmc: PMC9872315
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
Vascular Endothelial Growth Factor A
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
10Subventions
Organisme : Japan Society for the Promotion of Science
ID : 22K09285
Organisme : Japan Society for the Promotion of Science
ID : 22K09207
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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