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Transient but not permanent benefit of neuronal progenitor cell therapy after traumatic brain injury : potential causes and translational consequences
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Skardelly, Marco, Gaber, Khaled, Burdack, Swen, Scheidt, Franziska, Schuhmann, Martin U., Hilbig, Heidegard, Meixensberger, Jorgen and Boltze, Johannes (2014) Transient but not permanent benefit of neuronal progenitor cell therapy after traumatic brain injury : potential causes and translational consequences. Frontiers in Cellular Neuroscience, 8 . 318. doi:10.3389/fncel.2014.00318 ISSN 1662-5102.
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Official URL: http://dx.doi.org/10.3389/fncel.2014.00318
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.
Objectives: 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 × 105) into the putamen or systemically (5 × 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.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
| Journal or Publication Title: | Frontiers in Cellular Neuroscience | ||||
| Publisher: | Frontiers Research Foundation | ||||
| ISSN: | 1662-5102 | ||||
| Official Date: | October 2014 | ||||
| Dates: |
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| Volume: | 8 | ||||
| Article Number: | 318 | ||||
| DOI: | 10.3389/fncel.2014.00318 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Open Access (Creative Commons) |
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