AUTHOR=Skardelly Marco , Gaber Khaled , Burdack Swen , Scheidt Franziska , Schuhmann Martin U. , Hilbig Heidegard , Meixensberger Jürgen , Boltze Johannes 

TITLE=Transient but not permanent benefit of neuronal progenitor cell therapy after traumatic brain injury: potential causes and translational consequences

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=8

YEAR=2014

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2014.00318

DOI=10.3389/fncel.2014.00318

ISSN=1662-5102

ABSTRACT=<p><bold>Background</bold>: 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.</p><p><bold>Objectives</bold>: This study investigated the long-term (12 week) impact of human fetal neuronal progenitor cell (hNPC) transplantation 24 h after severe TBI in rats.</p><p><bold>Methods</bold>: Cells were either transplanted stereotactically (1 × 10<sup>5</sup>) into the putamen or systemically (5 × 10<sup>5</sup>) via the tail vein. Control animals received intravenous transplantation of vehicle solution.</p><p><bold>Results:</bold> An overall functional benefit was observed after systemic, but not local hNPC transplantation by area under the curve analysis (<italic>p</italic> &lt; 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 (<italic>p</italic> &lt; 0.05). Intracerebral hNPC transplantation slightly diminished astrogliosis in perilesional areas (<italic>p</italic> &lt; 0.01), but did not translate into a permanent functional benefit. No significant effects on angiogenesis were observed among the groups.</p><p><bold>Conclusion:</bold> 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.</p>