Human Amnion-Derived Multipotent Progenitor Cell Treatment Alleviates Traumatic Brain Injury-Induced Axonal Degeneration

Abstract

To identify a viable cell source with potential neuroprotective effects, we studied amnion-derived multipotent progenitor (AMP) cells in a rat model of penetrating ballistic-like brain injury (PBBI). AMP cells were labeled with fluorescent dye PKH26 and injected in rats immediately following right hemispheric PBBI or sham PBBI surgery by ipsilateral i.c.v. administration. At 2 weeks post-injury, severe necrosis developed along the PBBI tract and axonal degeneration was prominent along the corpus callosum (cc) and in the ipsilateral thalamus. Injected AMP cells first entered the subventricular zone (SVZ) in both sham and PBBI rats. Further AMP cell migration along the cc only occurred in PBBI animals. No significant difference in injury volume was observed across all treatment groups. In contrast, treatment with AMP cells significantly attenuated axonal degeneration in both the thalamus and the cc. Interestingly, PKH26-labeled AMP cells were detected only in the SVZ and the cc (in parallel with the axonal degeneration), but not in the thalamus. None of the labeled AMP cells appeared to express neural differentiation, as evidenced by the lack of double labeling with nestin, S-100, GFAP, and MAP-2 immunostaining. In conclusion, AMP cell migration was specifically induced by PBBI and requires SVZ homing, yet the neuroprotective effect of intracerebral ventrical treatment using AMP cells was not limited to the area where the cells were present. This suggests that the attenuation of the secondary brain injury following PBBI was likely to be mediated by mechanisms other than cell replacement, possibly through delivery or sustained secretion of neurotrophic factors.

A comparison of two cognitive test paradigms in a penetrating brain injury model

“…The size and location of the injury cavity at 7 days after injury is similar to that previously reported (Chen et al, 2009). Interestingly, the lesion showed no further enlargement by 21 days, suggesting that maximum lesion volume is reached within the first 7 days after injury and may explain the similar cognitive abilities of the animals at 7 and 21 days post-injury.…”

Animal models of traumatic brain injury

“…It induces marked white and grey matter damage, brain swelling, seizures, cortical spreading depression and neuroinflammation with a resulting sensorimotor impairment 112,115 . Therapeutic treatments including dextromethorphan and human amnion-derived multipotent progenitor cells have been recently evaluated in this model 116,117 .…”

Stem Cell Therapy in Brain Trauma: Implications for Repair and Regeneration of Injured Brain in Experimental TBI Models

“…Published data have reported that the use of human amnion-derived multipotent progenitor cells can significantly attenuate axonal degeneration and improve neurological function and brain tissue morphology of the injured rats (Chen et al, 2009;Yan et al, 2013). Intravenous administration of human adipose-derived stem cells or the derived culture medium into a controlled cortical impact rat model significantly improved motor and cognitive functions and reduced focal tissue damage and hippocampal cell loss (Tajiri et al, 2014).…”