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Transient but not permanent benefit of neuronal progenitor cell therapy after traumatic brain injury

Potential causes and translational consequences
: Skardelly, Marco; Gaber, Khaled; Burdack, Swen; Scheidt, Franziska; Schuhmann, Martin U.; Hilbig, Heidegard; Meixensberger, Jürgen; Boltze, Johannes

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Frontiers in cellular neuroscience. Online resource 8 (2014), Art. 318, 13 pp.
ISSN: 1662-5102
Journal Article, Electronic Publication
Fraunhofer IZI ()
neural progenitor cells; cell therapy; TBI; long-term functional outcome; translational research

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.
Objectives: This study investigated the long-term (12 week) impact of human fetal neuronal progenitor cell (hNPC) transplantation 24 h after severe TB I in rats.
Methods: Cells were either transplanted stereotactically (1 x 105) into the putamen or systemically (5 x 105) 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.
Conclusion: 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.