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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. 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 × 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. 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.

journal_name

Front Cell Neurosci

journal_title

Frontiers in cellular neuroscience

authors

Skardelly M,Gaber K,Burdack S,Scheidt F,Schuhmann MU,Hilbig H,Meixensberger J,Boltze J

doi

10.3389/fncel.2014.00318

subject

Has Abstract

pub_date

2014-10-14 00:00:00

pages

318

issn

1662-5102

journal_volume

pub_type

杂志文章

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