ArticlePloS one2015
Intra-Arterial Transplantation of Allogeneic Mesenchymal Stem Cells Mounts Neuroprotective Effects in a Transient Ischemic Stroke Model in Rats: Analyses of Therapeutic Time Window and Its Mechanisms.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 110 citations in OpenAlex.
- Salvaging the No-Reflow Zone: Intra-arterial Cranial Bone-Derived MSCs Restore Neurovascular Integrity After Stroke.Translational stroke research · 2026Article
- Mesenchymal stem cells and the central nervous system: historical perspectives and future directions.Frontiers in molecular neuroscience · 2026Review
- "Time Is Brain" - for Cell Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Modulation of epileptogenesis through transplantation of human mesenchymal stem cells with or without GDNF release.Cellular and molecular life sciences : CMLS · 2025Article
- Intra-Arterial Administration of Stem Cells and Exosomes for Central Nervous System Disease.International journal of molecular sciences · 2025Review
- The changes of digestive system inflammatory, oxidative stress, and histopathology factors following oral mesenchymal stem cells administration in rats with traumatic brain injury.BMC neuroscience · 2025Article
- Neuroprotection of Stem Cells Against Ischemic Brain Injury: From Bench to Clinic.Translational stroke research · 2024Review
- Article
- Probing Multiple Transplant Delivery Routes of CD+34 Stem Cells for Promoting Behavioral and Histological Benefits in Experimental Ischemic Stroke.Stem cells translational medicine · 2024Article
- Stem cell-based ischemic stroke therapy: Novel modifications and clinical challenges.Asian journal of pharmaceutical sciences · 2024Review
- Targeting Neurogenesis in Seeking Novel Treatments for Ischemic Stroke.Biomedicines · 2023Review
- The Efficiency of Neurospheres Derived from Human Wharton's Jelly Mesenchymal Stem Cells for Spinal Cord Injury Regeneration in Rats.International journal of molecular sciences · 2023Article
- 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.Stem cell research & therapy · 2023Article
- Article
- Transplantation of modified human bone marrow-derived stromal cells affords therapeutic effects on cerebral ischemia in rats.CNS neuroscience & therapeutics · 2022Article
- Establishment of longitudinal transcranial stimulation motor evoked potentials monitoring of the forelimbs and hindlimbs in an ischemic stroke rat model.Scientific reports · 2022Article
- Stem Cell Therapy for Sequestration of Traumatic Brain Injury-Induced Inflammation.International journal of molecular sciences · 2022Review
- Hotair and Malat1 Long Noncoding RNAs Regulate Bdnf Expression and Oligodendrocyte Precursor Cell Differentiation.Molecular neurobiology · 2022Article
- Stem Cell Transplantation Therapy and Neurological Disorders: Current Status and Future Perspectives.Biology · 2022Review
- The role of mesenchymal stem cell transplantation for ischemic stroke and recent research developments.Frontiers in neurology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveIntra-arterial stem cell transplantation exerts neuroprotective effects for ischemic stroke. However, the optimal therapeutic time window and mechanisms have not been completely understood. In this study, we investigated the relationship between the timing of intra-arterial transplantation of allogeneic mesenchymal stem cells (MSCs) in ischemic stroke model in rats and its efficacy in acute phase.
methodsAdult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes. MSCs (1 × 10(6) cells/ 1 ml PBS) were intra-arterially injected at either 1, 6, 24, or 48 hours (1, 6, 24, 48 h group) after MCAO. PBS (1 ml) was intra-arterially injected to control rats at 1 hour after MCAO. Behavioral test was performed immediately after reperfusion, and at 3, 7 days after MCAO using the Modified Neurological Severity Score (mNSS). Rats were euthanized at 7 days after MCAO for evaluation of infarct volumes and the migration of MSCs. In order to explore potential mechanisms of action, the upregulation of neurotrophic factor and chemotactic cytokine (bFGF, SDF-1α) induced by cell transplantation was examined in another cohort of rats that received intra-arterial transplantation at 24 hours after recanalization then euthanized at 7 days after MCAO for protein assays.
resultsBehavioral test at 3 and 7 days after transplantation revealed that stroke rats in 24h group displayed the most robust significant improvements in mNSS compared to stroke rats in all other groups (p's<0.05). Similarly, the infarct volumes of stroke rats in 24h group were much significantly decreased compared to those in all other groups (p's<0.05). These observed behavioral and histological effects were accompanied by MSC survival and migration, with the highest number of integrated MSCs detected in the 24h group. Moreover, bFGF and SDF-1α levels of the infarcted cortex were highly elevated in the 24h group compared to control group (p's<0.05).
conclusionsThese results suggest that intra-arterial allogeneic transplantation of MSCs provides post-stroke functional recovery and reduction of infarct volumes in ischemic stroke model of rats. The upregulation of bFGF and SDF-1α likely played a key mechanistic role in enabling MSC to afford functional effects in stroke. MSC transplantation at 24 hours after recanalization appears to be the optimal timing for ischemic stroke model, which should guide the design of clinical trials of cell transplantation for stroke patients.
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