Geburtshilfe Frauenheilkd 2018; 78(10): 221-222
DOI: 10.1055/s-0038-1671426
Poster
Freitag, 02.11.2018
Pränatal- und Geburtsmedizin II
Georg Thieme Verlag KG Stuttgart · New York

Intranasal administration of exosomes derived from Wharton's jelly mesenchymal stem cells to treat hypoxic-ischemic encephalopathy of prematurity

G Thomi
1  Inselspital, Bern University Hospital, Department of Obstetrics and Gynecology, Bern, Schweiz
2  University of Bern, Department of BioMedical Research, Bern, Schweiz
3  University of Bern, Graduate School for Cellular and Biomedical Sciences, Bern, Schweiz
,
M Joerger-Messerli
1  Inselspital, Bern University Hospital, Department of Obstetrics and Gynecology, Bern, Schweiz
2  University of Bern, Department of BioMedical Research, Bern, Schweiz
,
V Haesler
1  Inselspital, Bern University Hospital, Department of Obstetrics and Gynecology, Bern, Schweiz
2  University of Bern, Department of BioMedical Research, Bern, Schweiz
,
M Müller
1  Inselspital, Bern University Hospital, Department of Obstetrics and Gynecology, Bern, Schweiz
2  University of Bern, Department of BioMedical Research, Bern, Schweiz
4  Yale University School of Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, New Haven, Vereinigte Staaten von Amerika
,
A Schoeberlein
1  Inselspital, Bern University Hospital, Department of Obstetrics and Gynecology, Bern, Schweiz
2  University of Bern, Department of BioMedical Research, Bern, Schweiz
,
DV Surbek
1  Inselspital, Bern University Hospital, Department of Obstetrics and Gynecology, Bern, Schweiz
2  University of Bern, Department of BioMedical Research, Bern, Schweiz
› Author Affiliations
Further Information

Publication History

Publication Date:
20 September 2018 (online)

 

Survivors of preterm birth are at risk to develop hypoxic-ischemic encephalopathy (HIE) of prematurity. HIE is characterized by severe neuroinflammation leading to severe long-term disability. In animal models of HIE, Wharton's jelly mesenchymal stem cells (WJ-MSC) derived from umbilical cords can reduce neuroinflammation, in part because they release cell-derived extracellular vesicles like exosomes. We aimed to test the feasibility and the anti-inflammatory effects of intranasally administered WJ-MSC-derived exosomes in an animal model of HIE.

We isolated exosomes from WJ-MSC culture supernatants using serial centrifugation. Consistent with the etiology of HIE in preterm newborns, we introduced brain damage in 2-day old rats with lipopolysaccharide i.p. and unilateral carotid artery cautherization followed by hypoxia. As a treatment, rats received an intranasal administration of exosomes. To evaluate the feasibility of an intranasal exosome administration, we labeled and traced the exosomes inside the rats. To evaluate the anti-inflammatory effects of exosomes, we analyzed pro-inflammatory gene expression using real-time PCR.

Intranasally administered exosomes reached the brain already within 30 min after administration. A small portion of exosomes were detected within the lungs and the GI tract, but no exosomes were found in the spleen, likely excluding systemic absorption. Intranasal administration of exosomes dampened the upregulation of pro-inflammatory genes like tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1b and C-X-C motif chemokine 10 (P < 0.05) after experimental HIE.

Intranasal administration is a minimally invasive approach to deliver WJ-MSC-derived exosomes to the brain and represents a novel cell-free treatment for neuroinflammation after HIE of prematurity.