title: Nanotechnology versus stem cell engineering: in vitro comparison of neurite inductive potentials.
abstract: OBJECTIVE
  Innovative nerve conduits for peripheral nerve reconstruction are needed in order to specifically support peripheral nerve regeneration (PNR) whenever nerve autotransplantation is not an option. Specific support of PNR could be achieved by neurotrophic factor delivery within the nerve conduits via nanotechnology or stem cell engineering and transplantation.
  
  
  METHODS
  Here, we comparatively investigated the bioactivity of selected neurotrophic factors conjugated to iron oxide nanoparticles (np-NTFs) and of bone marrow-derived stem cells genetically engineered to overexpress those neurotrophic factors (NTF-BMSCs). The neurite outgrowth inductive activity was monitored in culture systems of adult and neonatal rat sensory dorsal root ganglion neurons as well as in the cell line from rat pheochromocytoma (PC-12) cell sympathetic culture model system.
  
  
  RESULTS
  We demonstrate that np-NTFs reliably support numeric neurite outgrowth in all utilized culture models. In some aspects, especially with regard to their long-term bioactivity, np-NTFs are even superior to free NTFs. Engineered NTF-BMSCs proved to be less effective in induction of sensory neurite outgrowth but demonstrated an increased bioactivity in the PC-12 cell culture system. In contrast, primary nontransfected BMSCs were as effective as np-NTFs in sensory neurite induction and demonstrated an impairment of neuronal differentiation in the PC-12 cell system.
  
  
  CONCLUSIONS
  Our results evidence that nanotechnology as used in our setup is superior over stem cell engineering when it comes to in vitro models for PNR. Furthermore, np-NTFs can easily be suspended in regenerative hydrogel matrix and could be delivered that way to nerve conduits for future in vivo studies and medical application.
authors.affiliation: Department of Clinical and Biological Sciences, Università Degli Studi di Torino, Orbassano, Piemonte, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Morano
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Lower-Saxony, Germany ; Center for Systems Neuroscience (ZSN), Hannover, Lower-Saxony, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Wrobel
authors.affiliation: Department of Clinical and Biological Sciences, Università Degli Studi di Torino, Orbassano, Piemonte, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Fregnan
authors.affiliation: NVR Research Ltd, Ness-Ziona, Israel.
authors.forename: Ofra
authors.initials: O
authors.lastname: Ziv-Polat
authors.affiliation: NVR Research Ltd, Ness-Ziona, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Shahar
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Lower-Saxony, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ratzka
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Lower-Saxony, Germany ; Center for Systems Neuroscience (ZSN), Hannover, Lower-Saxony, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Grothe
authors.affiliation: Department of Clinical and Biological Sciences, Università Degli Studi di Torino, Orbassano, Piemonte, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Geuna
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Hannover, Lower-Saxony, Germany ; Center for Systems Neuroscience (ZSN), Hannover, Lower-Saxony, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Haastert-Talini
mesh_terms: D000818:Animals; D060846:Cell Engineering / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D036103:Nanotechnology / Q000379:methods*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration; D016501:Neurites / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar; D044968:Regenerative Medicine
chemical_list: D058185:Magnetite Nanoparticles; D009414:Nerve Growth Factors
keywords: bone marrow-derived mesenchymal stem cells; conjugated neurotrophic factors; genetic cell engineering; iron oxide nanoparticles; neurite outgrowth