A pinboard by
Madison Paton

PhD Candidate, Hudson Institute of Medical Research


Investigating new therapies for babies born too soon to protect against cerebral palsy

Nearly 10% of all babies are born too early, or preterm. The majority of these babies have been exposed to infection during pregnancy affecting the placenta. Infection during pregnancy is a large contributor to the brain injury that leads to conditions like cerebral palsy. Unfortunately, there is no treatment or cure for these babies. This project investigates the potential of stem cell therapies to protect the brain after preterm delivery and exposure to inflammation.

Stem cells can be readily isolated from healthy placentas and contain a variety of cell types that would be ideal as a therapy against preterm brain inflammation. This project uses a preclinical model of brain injury, mimicking the type of brain injury that commonly occurs after preterm delivery. Stem cells are then administered at a critical time to see if they can protect the brain and prevent from life-long damage and disability.

To date, this project has shown that stem cells from healthy placentas provide protection against cell death, inflammation and loss of critical cell types that are essential for normal brain development.

Stem cell therapies show huge promise as a neonatal therapy for preterm brain inflammation. These results can help researchers and clinicians understand how stem cells can be used to prevent cerebral palsy.


Could cord blood cell therapy reduce preterm brain injury?

Abstract: Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP). Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain. Nearly 90% of preterm infants who later develop spastic CP have evidence of periventricular white matter injury. There are currently no treatments targeted at protecting the immature preterm brain. Umbilical cord blood (UCB) contains a diverse mix of stem and progenitor cells, and is a particularly promising source of cells for clinical applications, due to ethical and practical advantages over other potential therapeutic cell types. Recent studies have documented the potential benefits of UCB cells in reducing brain injury, particularly in rodent models of term neonatal hypoxia-ischemia. These studies indicate that UCB cells act via anti-inflammatory and immuno-modulatory effects, and release neurotrophic growth factors to support the damaged and surrounding brain tissue. The etiology of brain injury in preterm-born infants is less well understood than in term infants, but likely results from episodes of hypoperfusion, hypoxia-ischemia, and/or inflammation over a developmental period of white matter vulnerability. This review will explore current knowledge about the neuroprotective actions of UCB cells and their potential to ameliorate preterm brain injury through neonatal cell administration. We will also discuss the characteristics of UCB-derived from preterm and term infants for use in clinical applications.

Pub.: 28 Oct '14, Pinned: 25 Sep '17

Perinatal Brain Injury As a Consequence of Preterm Birth and Intrauterine Inflammation: Designing Targeted Stem Cell Therapies.

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.

Pub.: 27 Apr '17, Pinned: 25 Sep '17