ArticlePloS one2013
Mesenchymal stem cells induce T-cell tolerance and protect the preterm brain after global hypoxia-ischemia.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies.International journal of molecular sciences · 2021Pooled it
- Pooled it
- A Pilot Phase I Trial of Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells in Neonates With Hypoxic-Ischemic Encephalopathy.Stem cells translational medicine · 2023Trial
- Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices.Circulation · 2014Trial
- Stem cells redirect the neuroinflammatory trajectory of primed microglia in an ovine chorioamnionitis model.Brain, behavior, & immunity - health · 2026Article
- Mesenchymal Stem Cell (MSC)-based therapies for neonatal lung and brain injury - one size fits all?Molecular and cellular pediatrics · 2026Review
- Neuroimmune responses in neonatal hypoxic-ischemic encephalopathy: cellular roles, crosstalk, and therapeutic opportunities.Frontiers in pediatrics · 2026Review
- A systematic scoring system to optimise the testing of neurotherapeutics in models of perinatal brain injury, with an applied case study of human umbilical-cord MSC.Journal of neuroinflammation · 2025Article
- hUC-MSC extracellular vesicles protect against hypoxic-ischemic brain injury by promoting NLRP3 ubiquitination.Biomolecules & biomedicine · 2025Article
- Gold Mesoporous Silica-Coated Nanoparticles for Quantifying and Qualifying Mesenchymal Stem Cell Distribution; a Proof-of-Concept Study in Large Animals.ACS applied bio materials · 2025Article
- Boosting the Therapeutic Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells via Advanced Preconditioning for Neurodegenerative Disorders.Stem cells international · 2025Review
- Extracellular vesicles and preterm infant diseases.Frontiers in pediatrics · 2025Review
- Living biodrugs and how tissue source influences mesenchymal stem cell therapeutics for heart failure.World journal of cardiology · 2024Article
- Role of Microglial Modulation in Therapies for Perinatal Brain Injuries Leading to Neurodevelopmental Disorders.Advances in neurobiology · 2024Review
- Mononuclear cell therapy of neonatal hypoxic-ischemic encephalopathy in preclinical versus clinical studies: a systematic analysis of therapeutic efficacy and study design.Neuroprotection (Chichester, England) · 2023Article
- Extracellular vesicles from immortalized mesenchymal stromal cells protect against neonatal hypoxic-ischemic brain injury.Inflammation and regeneration · 2023Article
- Harnessing the therapeutic potential of the stem cell secretome in neonatal diseases.Seminars in perinatology · 2023Review
- Stem cell-based interventions for the prevention and treatment of intraventricular haemorrhage and encephalopathy of prematurity in preterm infants.The Cochrane database of systematic reviews · 2023Review
- Mesenchymal Stromal/Stem Cell Extracellular Vesicles and Perinatal Injury: One Formula for Many Diseases.Stem cells (Dayton, Ohio) · 2022Review
- Prenatal administration of multipotent adult progenitor cells modulates the systemic and cerebral immune response in an ovine model of chorioamnionitis.Brain, behavior, & immunity - health · 2022Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxic-ischemic encephalopathy (HIE) in preterm infants is a severe disease for which no curative treatment is available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play a pivotal role in the etiology of white matter injury, which is the clinical hallmark of HIE in preterm infants. The objective of this study was to assess the neuroprotective and anti-inflammatory effects of intravenously delivered mesenchymal stem cells (MSC) in an ovine model of HIE. In this translational animal model, global hypoxia-ischemia (HI) was induced in instrumented preterm sheep by transient umbilical cord occlusion, which closely mimics the clinical insult. Intravenous administration of 2 x 10(6) MSC/kg reduced microglial proliferation, diminished loss of oligodendrocytes and reduced demyelination, as determined by histology and Diffusion Tensor Imaging (DTI), in the preterm brain after global HI. These anti-inflammatory and neuroprotective effects of MSC were paralleled by reduced electrographic seizure activity in the ischemic preterm brain. Furthermore, we showed that MSC induced persistent peripheral T-cell tolerance in vivo and reduced invasion of T-cells into the preterm brain following global HI. These findings show in a preclinical animal model that intravenously administered MSC reduced cerebral inflammation, protected against white matter injury and established functional improvement in the preterm brain following global HI. Moreover, we provide evidence that induction of T-cell tolerance by MSC might play an important role in the neuroprotective effects of MSC in HIE. This is the first study to describe a marked neuroprotective effect of MSC in a translational animal model of HIE.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.