title: Cochlear nucleus whole mount explants promote the differentiation of neuronal stem cells from the cochlear nucleus in co-culture experiments.
abstract: The cochlear nucleus is the first brainstem nucleus to receive sensory input from the cochlea. Depriving this nucleus of auditory input leads to cellular and molecular disorganization which may potentially be counteracted by the activation or application of stem cells. Neuronal stem cells (NSCs) have recently been identified in the neonatal cochlear nucleus and a persistent neurogenic niche was demonstrated in this brainstem nucleus until adulthood. The present work investigates whether the neurogenic environment of the cochlear nucleus can promote the survival of engrafted NSCs and whether cochlear nucleus-derived NSCs can differentiate into neurons and glia in brain tissue. Therefore, cochlear nucleus whole-mount explants were co-cultured with NSCs extracted from either the cochlear nucleus or the hippocampus and compared to a second environment using whole-mount explants from the hippocampus. Factors that are known to induce neuronal differentiation were also investigated in these NSC-explant experiments. NSCs derived from the cochlear nucleus engrafted in the brain tissue and differentiated into all cells of the neuronal lineage. Hippocampal NSCs also immigrated in cochlear nucleus explants and differentiated into neurons, astrocytes and oligodendrocytes. Laminin expression was up-regulated in the cochlear nucleus whole-mounts and regulated the in vitro differentiation of NSCs from the cochlear nucleus. These experiments confirm a neurogenic environment in the cochlear nucleus and the capacity of cochlear nucleus-derived NSCs to differentiate into neurons and glia. Consequently, the presented results provide a first step for the possible application of stem cells to repair the disorganization of the cochlear nucleus, which occurs after hearing loss.
authors.affiliation: Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery and the Comprehensive Hearing Center, University of Wuerzburg, Wuerzburg, Germany. Electronic address: Rak_K@ukw.de.
authors.forename: Kristen
authors.initials: K
authors.lastname: Rak
authors.affiliation: Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery and the Comprehensive Hearing Center, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Völker
authors.affiliation: Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery and the Comprehensive Hearing Center, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Jürgens
authors.affiliation: Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery and the Comprehensive Hearing Center, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Völker
authors.affiliation: Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery and the Comprehensive Hearing Center, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Frenz
authors.affiliation: Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery and the Comprehensive Hearing Center, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Agmal
authors.initials: A
authors.lastname: Scherzad
authors.affiliation: Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery and the Comprehensive Hearing Center, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schendzielorz
authors.affiliation: Institute for Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Jablonka
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery "Otto Körner", Rostock University Medical Center, Rostock, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Mlynski
authors.affiliation: Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery and the Comprehensive Hearing Center, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Radeloff
authors.affiliation: Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery and the Comprehensive Hearing Center, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hagen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D017626:Cochlear Nucleus / Q000166:cytology*; D018920:Coculture Techniques; D004815:Epidermal Growth Factor / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007797:Laminin / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D009419:Nerve Tissue Proteins; D004815:Epidermal Growth Factor
keywords: Co-culture; Cochlear nucleus; DiI; Differentiation; Hippocampus; Laminin; Neuronal stem cells