title: Intranasal delivery of cells to the brain.
abstract: The safety and efficacy of cell-based therapies for neurodegenerative diseases depends on the mode of cell administration. We hypothesized that intranasally administered cells could bypass the blood-brain barrier by migrating from the nasal mucosa through the cribriform plate along the olfactory neural pathway into the brain and cerebrospinal fluid (CSF). This would minimize or eliminate the distribution of cellular grafts to peripheral organs and will help to dispense with neurosurgical cell implantation. Here we demonstrate transnasal delivery of cells to the brain following intranasal application of fluorescently labeled rat mesenchymal stem cells (MSC) or human glioma cells to naive mice and rats. After cells crossed the cribriform plate, two migration routes were identified: (1) migration into the olfactory bulb and to other parts of the brain; (2) entry into the CSF with movement along the surface of the cortex followed by entrance into the brain parenchyma. The delivery of cells was enhanced by hyaluronidase treatment applied intranasally 30 min prior to the application of cells. Intranasal delivery provides a new non-invasive method for cell delivery to the CNS.
authors.affiliation: Department of Clinical Pharmacology, University Hospital of Tuebingen, Otfried-Mueller Str. 45, D-72076 Tuebingen, Germany. lusine.danielyan@med.uni-tuebingen.de
authors.forename: Lusine
authors.initials: L
authors.lastname: Danielyan
authors.forename: Richard
authors.initials: R
authors.lastname: Schäfer
authors.forename: Andreas
authors.initials: A
authors.lastname: von Ameln-Mayerhofer
authors.forename: Marine
authors.initials: M
authors.lastname: Buadze
authors.forename: Julia
authors.initials: J
authors.lastname: Geisler
authors.forename: Tim
authors.initials: T
authors.lastname: Klopfer
authors.forename: Ute
authors.initials: U
authors.lastname: Burkhardt
authors.forename: Barbara
authors.initials: B
authors.lastname: Proksch
authors.forename: Stephan
authors.initials: S
authors.lastname: Verleysdonk
authors.forename: Miriam
authors.initials: M
authors.lastname: Ayturan
authors.forename: Gayane H
authors.initials: GH
authors.lastname: Buniatian
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Gleiter
authors.forename: William H
authors.initials: WH
authors.lastname: Frey