Key words: Preterm brain injury, therapy, bone marrow derived stem cells, Annexin A1

"Protection of the preterm brain against inflammatory stress: A promising role for stem cellbased therapy and Annexin A1"

The thesis covers the health issue prematurity. Usually pregnancy takes 40 weeks. Prematurity is defined by birth before the 37th week of pregnancy. Being born preterm and underlying reasons for spontaneous birth such as infection of the amniotic sac predisposes the preterm born baby to brain injury, called encephalopathy of prematurity. This thesis investigated whether bone marrow derived stem cells and factors produced by stem cells (e.g. a protein called Annexin A1) could improve brain outcome in preterm stress models. The hypothesis was that the therapy modulates therapeutic targets that are less functional following preterm stress. Therapeutic targets are: 1) resident immune cells of the brain, 2) the barrier protecting the brain from the periphery and 3) the peripheral immune system. It was found that Annexin A1 is lost in the brain barrier upon preterm stress and protects brain barrier stability when administered. Further, it improves brain outcome after intranasal administration and is one of the proteins that is enhanced present in immune cells and the brain barrier after preterm stress and stem cell therapy, potentially to protect the brain from future injurious hits. Consequently, stem cells and their secreted products, such as Annexin A1, are an interesting candidate to further optimize in order to improve the lives of preterm born babies.

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