Long-term administration of amnion-derived cellular cytokine suspension promotes functional recovery in a model of penetrating ballistic-like brain injury

Ying Deng-Bryant*, Zhiyong Chen, Christopher Van Der Merwe, Zhilin Liao, Jitendra R. Dave, Randall Rupp, Deborah A. Shear, Frank C. Tortella

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Background: Previous work has shown that human amnion-derived progenitor (AMP) cell therapy is neuroprotective in a penetrating ballistic-like brain injury (PBBI) model. However, the neuroprotective capacity of AMP cells seemed to be mediated by the sustained secretion of AMP cell-derived neurotrophic factors, which are abundant in the amnion-derived cellular cytokine suspension (ACCS). To test this theory, the current study assessed the neuroprotective efficacy of long-term ACCS delivery in the PBBI model. Methods: Experiment 1 assessed the bioactive stability and neuroprotective capacity of ACCS in an in vitro model of neurodegeneration. Experiment 2 evaluated the therapeutic effects of ACCS delivery initiated 15 minutes after PBBI and continued for 2 weeks after injury. Experiment 3 was designed to identify the therapeutic window for long-term ACCS delivery in the PBBI model. Outcome metrics included neurobehavioral assessments and neuropathologic measures of neuroinflammation and axonal/neuronal degeneration. Results: Experiment 1 demonstrated that ACCS is thermally stable for 1 week at 37°C and that ACCS treatment protected neurite against staurosporine toxicity. Experiment 2 identified the optimal infusion rate of ACCS (1 μL/h) and demonstrated that long-term infusion of ACCS was capable of promoting significant protection against PBBI-induced neuropathology and motor abnormalities, but was not sufficient for reducing cognitive deficits. Finally, the results of Experiment 3 showed that ACCS is effective in promoting significant neuroprotection even when onset of treatment is delayed out to 24 hours (but not 48 hours) after PBBI. Conclusions: Collectively, our results support the hypothesis that the neuroprotective effects of AMP cells are mediated through a sustained delivery of ACCS, which implicates ACCS as a promising neuroprotection agent for clinical study.

Original languageEnglish
Pages (from-to)S156-S164
JournalJournal of Trauma and Acute Care Surgery
Issue number2 SUPPL. 1
StatePublished - Aug 2012
Externally publishedYes


  • Penetrating ballistic-like brain injury
  • amnion-derived cellular cytokine suspension
  • glial fibrillary acidic protein
  • rotarod
  • silver stain


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