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Perinatal Brain Injury As a Consequence of Preterm Birth and Intrauterine Inflammation: Designing Targeted Stem Cell
Madison C B Paton1,2, Courtney A McDonald1, Beth J Allison1
1Neurodevelopment and Neuroprotection Research Group, The Ritchie Centre, Hudson Institute of Medical Research, Monash UniversityClayton, VIC, Australia.
Insights
Chorioamnionitis causes preterm birth and brain injury. Stem cell therapies, particularly mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), show promise for treating inflammation and repairing brain damage in affected infants.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Obstetrics
Background:
- Chorioamnionitis, an infection of the fetal membranes, is a primary driver of preterm birth and subsequent fetal brain injury.
- This intrauterine infection triggers a fetal inflammatory response, leading to severe neurological deficits and cerebral palsy.
- Current treatments lack the ability to prevent or repair brain damage in preterm infants affected by intrauterine infection.
Purpose of the Study:
- To review the cascade of brain injury in preterm infants following fetal inflammatory events.
- To identify critical periods of vulnerability in the developing fetal brain.
- To explore the potential of cell-based therapies, specifically stem cells, for neuroprotection and repair.
Main Methods:
- Review of existing literature on chorioamnionitis, preterm brain injury, and stem cell therapies.
- Analysis of the mechanisms underlying fetal inflammatory response and its impact on the brain.
- Evaluation of the potential benefits of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs).
Main Results:
- Mesenchymal stem cells (MSCs) possess significant immunomodulatory properties, crucial for mitigating neuroinflammation.
- Endothelial progenitor cells (EPCs) offer angiogenic and vascular repair capabilities, vital for restoring brain vasculature.
- A combined MSC and EPC therapy presents a promising strategy for addressing both inflammation and vascular damage.
Conclusions:
- Stem cell therapies, derived from umbilical cord blood and tissue, are emerging as a safe and potentially effective treatment for preterm brain injury.
- Further investigation into combined MSC and EPC therapy is warranted to target inflammation and promote neurovascular repair in preterm infants.
- Identifying the most efficacious stem cell types is crucial for optimizing therapeutic outcomes in cerebral palsy.
Abstract:
Chorioamnionitis is a major cause of preterm birth and brain injury. Bacterial invasion of the chorion and amnion, and/or the placenta, can lead to a fetal inflammatory response, which in turn has significant adverse consequences for the developing fetal brain. Accordingly, there is a strong causal link between chorioamnionitis, preterm brain injury and the pathogenesis of severe postnatal neurological deficits and cerebral palsy. Currently there are no treatments to protect or repair against brain injury in preterm infants born after pregnancy compromised by intrauterine infection. This review describes the injurious cascade of events in the preterm brain in response to a severe fetal inflammatory event. We will highlight specific periods of increased vulnerability, and the potential effects of therapeutic intervention with cell-based therapies. Many clinical trials are underway to investigate the efficacy of stem cells to treat patients with cerebral palsy. Stem cells, obtained from umbilical cord tissue and cord blood, normally discarded after birth, are emerging as a safe and potentially effective therapy. It is not yet known, however, which stem cell type(s) are the most efficacious for administration to preterm infants to treat brain injury-mediated inflammation. Individual stem cell populations found in cord blood and tissue, such as mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), have a number of potential benefits that may specifically target preterm inflammatory-induced brain injury. MSCs have strong immunomodulatory potential, protecting against global and local neuroinflammatory cascades triggered during infection to the fetus. EPCs have angiogenic and vascular reparative qualities that make them ideal for neurovascular repair. A combined therapy using both MSCs and EPCs to target inflammation and promote angiogenesis for re-establishment of vital vessel networks is a treatment concept that warrants further investigation.
