title: Intranasal delivery of neural stem/progenitor cells: a noninvasive passage to target intracerebral glioma.
abstract: Stem cell-based therapies for neurological disorders, including brain tumors, advance continuously toward clinical trials. Optimized cell delivery to the central nervous system remains a challenge since direct intracerebral injection is an invasive method with low transplantation efficiency. We investigated the feasibility of intranasal administration of neural stem/progenitor cells (NSPCs) as an alternative, noninvasive, and direct passage for the delivery of stem cells to target malignant gliomas. Tumor-targeting and migratory pathways of murine and human NSPCs were investigated by intravital magnetic resonance imaging and in histological time course analyses in the intracerebral U87, NCE-G55T2, and syngenic Gl261 glioblastoma models. Intranasally administered NSPCs displayed a rapid, targeted tumor tropism with significant numbers of NSPCs accumulating specifically at the intracerebral glioma site within 6 hours after intranasal delivery. Histological time series analysis revealed that NSPCs migrated within the first 24 hours mainly via olfactory pathways but also by systemic distribution via the microvasculature of the nasal mucosa. Intranasal application of NSPCs leads to a rapid, targeted migration of cells toward intracerebral gliomas. The directional distribution of cells accumulating intra- and peritumorally makes the intranasal delivery of NSPCs a promising noninvasive and convenient alternative delivery method for the treatment of malignant gliomas with the possibility of multiple dosing regimens.
authors.affiliation: Department of Neurosurgery, Medical Center, Eppendorf, Hamburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Reitz
authors.forename: Maria
authors.initials: M
authors.lastname: Demestre
authors.forename: Jan
authors.initials: J
authors.lastname: Sedlacik
authors.forename: Hildegard
authors.initials: H
authors.lastname: Meissner
authors.forename: Jens
authors.initials: J
authors.lastname: Fiehler
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.forename: Nils Ole
authors.initials: NO
authors.lastname: Schmidt
mesh_terms: D000281:Administration, Intranasal / Q000379:methods*; D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology; D005625:Frontal Lobe / Q000166:cytology; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D010296:Parietal Lobe / Q000166:cytology; D033581:Stem Cell Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous