title: BDNF increases survival and neuronal differentiation of human neural precursor cells cotransplanted with a nanofiber gel to the auditory nerve in a rat model of neuronal damage.
abstract: OBJECTIVE
  To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation.
  
  
  METHODS
  We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM). Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel), in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact.
  
  
  RESULTS
  Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus.
  
  
  CONCLUSIONS
  Our results indicate that human neural precursor cells (HNPC) integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF) treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN).
authors.affiliation: Center for Hearing and Communication Research, Karolinska University Hospital, 171 76 Stockholm, Sweden ; Department of Clinical Sciences, Intervention and Technology (CLINTEC), Section of Otorhinolaryngology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden ; Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Center for Hearing and Communication Research, Karolinska University Hospital, 171 76 Stockholm, Sweden ; Department of Clinical Sciences, Intervention and Technology (CLINTEC), Section of Otorhinolaryngology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Palmgren
authors.affiliation: Center for Hearing and Communication Research, Karolinska University Hospital, 171 76 Stockholm, Sweden ; Department of Clinical Sciences, Intervention and Technology (CLINTEC), Section of Otorhinolaryngology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Novozhilova
authors.affiliation: Department of Ophthalmology, Institution of Clinical Sciences in Lund, Lund University, 221 84 Lund, Sweden.
authors.forename: Ulrica
authors.initials: U
authors.lastname: Englund Johansson
authors.affiliation: Center for Hearing and Communication Research, Karolinska University Hospital, 171 76 Stockholm, Sweden ; Department of Clinical Sciences, Intervention and Technology (CLINTEC), Section of Otorhinolaryngology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Spieles-Engemann
authors.affiliation: Center for Hearing and Communication Research, Karolinska University Hospital, 171 76 Stockholm, Sweden ; Department of Clinical Sciences, Intervention and Technology (CLINTEC), Section of Otorhinolaryngology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kale
authors.affiliation: Departments of Chemistry, Materials Science and Engineering, and Medicine and Institute for Bionanotechnology in Medicine, Northwestern University, Chicago, IL 60208, USA.
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Stupp
authors.affiliation: Department of Clinical Sciences, Intervention and Technology (CLINTEC), Section of Otorhinolaryngology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden ; Division of Otorhinolaryngology, Linköping University Hospital, 581 85 Linköping, Sweden ; Division of Otorhinolaryngology, Department of Clinical and Experimental Medicine, University of Linköping, 581 85 Linköping, Sweden.
authors.forename: Petri
authors.initials: P
authors.lastname: Olivius
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003056:Cochlear Nerve / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005782:Gels / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D057139:Nanofibers / Q000737:chemistry*; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005782:Gels; D049452:Green Fluorescent Proteins