title: Transient but not permanent benefit of neuronal progenitor cell therapy after traumatic brain injury: potential causes and translational consequences.
abstract: BACKGROUND
  Numerous studies have reported a beneficial impact of neural progenitor cell transplantation on functional outcome after traumatic brain injury (TBI) during short and medium follow-up periods. However, our knowledge regarding long-term functional effects is fragmentary while a direct comparison between local and systemic transplantation is missing so far.
  
  
  OBJECTIVE
  This study investigated the long-term (12 week) impact of human fetal neuronal progenitor cell (hNPC) transplantation 24 h after severe TBI in rats.
  
  
  METHODS
  Cells were either transplanted stereotactically (1 × 10(5)) into the putamen or systemically (5 × 10(5)) via the tail vein. Control animals received intravenous transplantation of vehicle solution.
  
  
  RESULTS
  An overall functional benefit was observed after systemic, but not local hNPC transplantation by area under the curve analysis (p < 0.01). Surprisingly, this effect vanished during later stages after TBI with all groups exhibiting comparable functional outcomes 84 days after TBI. Investigation of cell-mediated inflammatory processes revealed increasing microglial activation and macrophage presence during these stages, which was statistically significant after systemic cell administration (p < 0.05). Intracerebral hNPC transplantation slightly diminished astrogliosis in perilesional areas (p < 0.01), but did not translate into a permanent functional benefit. No significant effects on angiogenesis were observed among the groups.
  
  
  CONCLUSIONS
  Our results suggest the careful long-term assessment of cell therapies for TBI, as well as to identify potential long-term detrimental effects of such therapies before moving on to clinical trials. Moreover, immunosuppressive protocols, though widely used, should be rigorously assessed for their applicability in the respective setup.
authors.affiliation: Department of Neurosurgery, University of Leipzig Leipzig, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Skardelly
authors.affiliation: Department of Neurosurgery, University of Leipzig Leipzig, Germany.
authors.forename: Khaled
authors.initials: K
authors.lastname: Gaber
authors.affiliation: Department of Neurosurgery, University of Leipzig Leipzig, Germany.
authors.forename: Swen
authors.initials: S
authors.lastname: Burdack
authors.affiliation: Department of Neurosurgery, University of Leipzig Leipzig, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Scheidt
authors.affiliation: Department of Neurosurgery, University of Leipzig Leipzig, Germany.
authors.forename: Martin U
authors.initials: MU
authors.lastname: Schuhmann
authors.affiliation: Institute of Anatomy, University of Leipzig Leipzig, Germany.
authors.forename: Heidegard
authors.initials: H
authors.lastname: Hilbig
authors.affiliation: Department of Neurosurgery, University of Leipzig Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Meixensberger
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology and Translational Centre for Regenerative Medicine, University of Leipzig Leipzig, Germany ; Stroke and Neurovascular Regulation Laboratory, Massachussets General Hospital and Harvard Medical School Charlestown, MA, USA.
authors.forename: Johannes
authors.initials: J
authors.lastname: Boltze
keywords: TBI; cell therapy; long-term functional outcome; neural progenitor cells; translational research