title: Intranasal Delivery of Umbilical Cord-Derived Mesenchymal Stem Cells Preserves Myelination in Perinatal Brain Damage.
abstract: Preterm white matter injury (WMI) is an important cause for long-term disability. Stem cell transplantation has been proposed as a novel therapeutic approach. However, intracerebral transplantation is not feasible for clinical purpose in newborns. Intranasal delivery of cells to the brain might be a promising, noninvasive therapeutic approach to restore the damaged brain. Therefore, our goal is to study the remyelinating potential of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) after intranasal delivery. Wistar rat pups, previously brain-damaged by a combined hypoxic-ischemic and inflammatory insult, received hWJ-MSC (150,000 cells in 3 μL) that were intranasally delivered twice to each nostril (600,000 cells total). WMI was assessed by immunohistochemistry and western blot for myelination, astrogliosis, and microgliosis. The expression of preoligodendrocyte markers, and neurotrophic factors, was analyzed by real-time polymerase chain reaction. Animals treated with intranasally delivered hWJ-MSC showed increased myelination and decreased gliosis compared to untreated animals. hWJ-MSC may, therefore, modulate the activation of microglia and astrocytes, resulting in a change of the brain microenvironment, which facilitates the maturation of oligodendrocyte lineage cells. This is the first study to show that intranasal delivery of hWJ-MSC in rats prevented hypomyelination and microgliosis in a model of WMI in the premature rat brain. Further studies should address the dose and frequency of administration.
authors.affiliation: 1 Department of Obstetrics and Gynecology, University Hospital Bern , Bern, Switzerland .|2 Laboratory for Prenatal Medicine, Department of Clinical Research, University of Bern , Bern, Switzerland .|3 Graduate School for Biomedical Sciences (GCB), University of Bern , Bern, Switzerland .
authors.forename: Byron
authors.initials: B
authors.lastname: Oppliger
authors.affiliation: 1 Department of Obstetrics and Gynecology, University Hospital Bern , Bern, Switzerland .|2 Laboratory for Prenatal Medicine, Department of Clinical Research, University of Bern , Bern, Switzerland .
authors.forename: Marianne
authors.initials: M
authors.lastname: Joerger-Messerli
authors.affiliation: 1 Department of Obstetrics and Gynecology, University Hospital Bern , Bern, Switzerland .|2 Laboratory for Prenatal Medicine, Department of Clinical Research, University of Bern , Bern, Switzerland .|4 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine , New Haven, Connecticut.
authors.forename: Martin
authors.initials: M
authors.lastname: Mueller
authors.affiliation: 1 Department of Obstetrics and Gynecology, University Hospital Bern , Bern, Switzerland .|2 Laboratory for Prenatal Medicine, Department of Clinical Research, University of Bern , Bern, Switzerland .
authors.forename: Ursula
authors.initials: U
authors.lastname: Reinhart
authors.affiliation: 1 Department of Obstetrics and Gynecology, University Hospital Bern , Bern, Switzerland .|2 Laboratory for Prenatal Medicine, Department of Clinical Research, University of Bern , Bern, Switzerland .
authors.forename: Philipp
authors.initials: P
authors.lastname: Schneider
authors.affiliation: 1 Department of Obstetrics and Gynecology, University Hospital Bern , Bern, Switzerland .|2 Laboratory for Prenatal Medicine, Department of Clinical Research, University of Bern , Bern, Switzerland .
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Surbek
authors.affiliation: 1 Department of Obstetrics and Gynecology, University Hospital Bern , Bern, Switzerland .|2 Laboratory for Prenatal Medicine, Department of Clinical Research, University of Bern , Bern, Switzerland .
authors.forename: Andreina
authors.initials: A
authors.lastname: Schoeberlein
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D001930:Brain Injuries / Q000150:complications / Q000473:pathology / Q000628:therapy*; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology / Q000628:therapy; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology / Q000628:therapy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009186:Myelin Sheath / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism; D009836:Oligodendroglia / Q000473:pathology; D017208:Rats, Wistar; D014470:Umbilical Cord / Q000166:cytology*; D066127:White Matter / Q000473:pathology
chemical_list: D015415:Biomarkers; D009414:Nerve Growth Factors