Journal
FRONTIERS IN CELLULAR NEUROSCIENCE
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2014.00318
Keywords
neural progenitor cells; cell therapy; TBI; long-term functional outcome; translational research
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Funding
- funds of the Free State of Saxony distributed by the University of Leipzig [1-56]
- Deutsche Forschungsgemeinschaft
- Open Access Publishing Fund of Tuebingen University
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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.
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