TY - JOUR
T1 - Long-term administration of amnion-derived cellular cytokine suspension promotes functional recovery in a model of penetrating ballistic-like brain injury
AU - Deng-Bryant, Ying
AU - Chen, Zhiyong
AU - Van Der Merwe, Christopher
AU - Liao, Zhilin
AU - Dave, Jitendra R.
AU - Rupp, Randall
AU - Shear, Deborah A.
AU - Tortella, Frank C.
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Penetrating ballistic-like brain injury
KW - amnion-derived cellular cytokine suspension
KW - glial fibrillary acidic protein
KW - rotarod
KW - silver stain
UR - http://www.scopus.com/inward/record.url?scp=84864632202&partnerID=8YFLogxK
U2 - 10.1097/TA.0b013e3182625f5f
DO - 10.1097/TA.0b013e3182625f5f
M3 - Article
C2 - 22847087
AN - SCOPUS:84864632202
SN - 2163-0755
VL - 73
SP - S156-S164
JO - Journal of Trauma and Acute Care Surgery
JF - Journal of Trauma and Acute Care Surgery
IS - 2 SUPPL. 1
ER -