Oppliger, Byron; Jörger Messerli, Marianne; Müller, Martin; Reinhart, Ursula; Schneider, Philipp; Surbek, Daniel; Schoeberlein, Andreina (March 2017). Effects of Single or Repeated Intranasal Administration of Umbilical Cord Stem Cells in Neonatal Rats with Hypoxic-Ischemic Brain Lesions. Reproductive sciences, 24(Suppl 1), 300A-300A. Sage
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INTRODUCTION: Lately, there has been a significant increase in preterm-specific brain injuries that still remain an unresolved clinical issue. The majority of the infants born preterm with brain injuries develop non-cystic, diffuse white matter injury (WMI), characterized by an overall hypomyelination of the brain. Preterm brain injury is an important cause for long-term disability. To date, no cure has been found to treat such lesions. Intranasal delivery of Wharton’s jelly mesenchymal stem cells (WJ-MSC) might be the ideal, non-invasive therapeutic approach to restore the damaged brain. Therefore, our goal is to find an optimal treatment regimen of intranasally delivered WJ-MSC to achieve a maximum recovery after brain injury.
METHODS: WJ-MSC (84’000 cells/ml) were delivered intranasally to Wistar rat pups that were previously brain-damaged (total 1*106 cells). Rat pups received either one, two or three treatments, at two days intervals. Animals were sacrificed 7 days after the first application of the cells. Fixed brains were analyzed by immunohistochemistry and real-time PCR.
RESULTS: Treatment with WJ-MSC increased myelination and decreased astro- and microgliosis. Repeated intranasal delivery was not more effective than single treatment, as assessed by immunohistochemistry. However, multiple administrations increased significantly the expression of brain-derived neurotrophic factor (Bdnf) compared to single administration.
CONCLUSIONS: In conclusion, intranasal delivery of WJ-MSC to the newborn after preterm brain damage has a neuroregenerative potential, which is probably mediated by a decreased astro- and microgliosis and an increased expression of important neurotrophic factors like Bdnf. Intranasal delivery of stem cells to the brain is an efficient and non-invasive method for stem cell treatment of perinatal brain damage.
Financial support by Cryosave Switzerland, Mobiliar Jubiläumsstiftung, Switzerland and The Eagle Foundation, Switzerland.
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