title: Human adipose-derived mesenchymal stromal cells increase endogenous neurogenesis in the rat subventricular zone acutely after 6-hydroxydopamine lesioning.
abstract: OBJECTIVE
  In Parkinson's disease (PD), neurogenesis in the subventricular zone (SVZ)-olfactory bulb (OB) axis is affected as the result of the lack of dopaminergic innervations reaching the SVZ. This aberrant network has been related to the hyposmia of PD patients, which is an early diagnostic marker of the disease. Consequently, much interest arose in finding mechanisms to modulate the SVZ-OB axis. Direct modulation of this axis could be achieved by transplantation of mesenchymal stromal cells (MSC), as it has been shown in rat and mouse PD models. However, the neurogenic effect of MSC in PD was thus far only analyzed weeks after transplantation, and little is known about effects immediately after transplantation.
  
  
  METHODS
  We assessed the acute neuroprotective and neurogenic effects of adipose-derived MSC transplanted into the rat substantia nigra in the 6-hydroxydopamine model of PD.
  
  
  RESULTS
  Three days after transplantation, subventricular neurogenesis was significantly increased in MSC-transplanted versus non-transplanted animals. Most MSC were found in the region of the substantia nigra and the surrounding arachnoid mater, expressing S100β and brain-derived neurotrophic factor, whereas some MSC showed an endothelial phenotype and localized around blood vessels.
  
  
  CONCLUSIONS
  The acute neurogenic effects and neurotrophic factor expression of MSC could help to restore the SVZ-OB axis in PD.
authors.affiliation: Department of Neurology, Charité University Medicine, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Schwerk
authors.affiliation: Department of Neurology, Charité University Medicine, Berlin, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Altschüler
authors.affiliation: Berlin-Brandenburg Centre for Regenerative Therapies, Charité University Medicine, Berlin, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Roch
authors.affiliation: Institute of Biomaterial Science and Berlin-Brandenburg Centre for Regenerative Therapies, Helmholtz-Zentrum Geesthacht, Teltow, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Gossen
authors.affiliation: Department of Psychiatry, Technical University Dresden, Dresden, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
authors.affiliation: Department of Neurology, Charité University Medicine, Berlin, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Berg
authors.affiliation: Berlin-Brandenburg Centre for Regenerative Therapies, Charité University Medicine, Berlin, Germany; Seoul National University, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul, Republic of Korea.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kurtz
authors.affiliation: Department of Neurology, Charité University Medicine, Berlin, Germany. Electronic address: barbara.steiner@charite.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Steiner
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020547:Lateral Ventricles / Q000166:cytology / Q000254:growth & development*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology*; D009765:Obesity / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology; D016627:Oxidopamine / Q000009:adverse effects; D010300:Parkinson Disease / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit / Q000096:biosynthesis; D013378:Substantia Nigra / Q000166:cytology; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; D016627:Oxidopamine
keywords: Parkinson's disease; adult stem cells; mesenchymal stromal cells; neurogenesis; plasticity; regeneration