Umbilical Cord Stem Cell-Derived Exosomes as a Treatment in Hypoxic-Ischemic Brain Injury.

Thomi, Gierin Florence; Jörger Messerli, Marianne; Haesler, Valérie; Surbek, Daniel; Schoeberlein, Andreina (March 2019). Umbilical Cord Stem Cell-Derived Exosomes as a Treatment in Hypoxic-Ischemic Brain Injury. Reproductive sciences, 26(Suppl 1), 113A-114A. Sage

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Introduction: Survivors of preterm birth are at risk to suffer from hypoxic-ischemic brain injury leading to subsequent neurodevelopmental deficits. Preterm-specific hypoxic-ischemic brain injury is characterized by a disruption of normal developmental myelination of the brain. In animal models of hypoxic-ischemic brain injury, Wharton’s jelly mesenchymal stem/stromal cells (WJ-MSC) derived from umbilical cords restore normal myelination, in part through the release of cell-derived extracellular vesicles like exosomes. We aimed to test the therapeutic potential of WJ-MSC-derived in an animal model of hypoxic-ischemic brain injury.
Methods: We isolated exosomes from WJ-MSC culture supernatants using serial centrifugation. Consistent with the etiology of hypoxic-ischemic brain injury in preterm infants, we introduced brain injury in 3-day old rat pups with lipopolysaccharide i.p. and unilateral carotid artery cauterization followed by hypoxia (8% O2). As a treatment, animals received an intranasal administration of WJ-MSC-derived exosomes. In a short-term experiment, we analyzed cortical apoptosis and myelination using TUNEL-assay, real-time RT-PCR and Western blot. In a long-time experiment, we tracked the survival and learning capacity of the animals using the Morris water maze assay.
Results: Treated animals exhibited reduced cortical apoptosis and diminished hypomyelination 9 days after brain injury as the exosomes rescued the loss of myelin basic protein (p<0.05). Exosome treatment doubled the animal’s overall survival rate (p<0.01) and improved their learning capacity (p<0.05) 1 month after hypoxic-ischemic brain injury.
Conclusion: Treatment with WJ-MSC-derived exosomes improves survival, partially restores normal developmental myelination and alleviates associated neurodevelopmental deficits. Intranasal administration of WJ-MSC-derived exosomes represents a minimally-invasive and effective treatment for hypoxic-ischemic brain injury.

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