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Ex-Vivo Uterine Environment (EVE) Therapy Induced Limited Fetal Inflammation in a Premature Lamb Model.

Miura Y, Saito M, Usuda H, Woodward E, Rittenschober-Böhm J, Kannan PS, Musk GC, Matsuda T, Newnham JP, Kemp MW - PLoS ONE (2015)

Bottom Line: Meanwhile, elevations in fetal inflammation are associated with adverse neonatal outcomes.There was no significant difference (p>0.05) in surfactant protein mRNA expression level between the two groups.Despite this, EVE therapy only induced a modest fetal inflammatory response and did not promote lung maturation.

View Article: PubMed Central - PubMed

Affiliation: School of Women's and Infants' Health, The University of Western Australia, Crawley, Western Australia, Australia; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan.

ABSTRACT

Introduction: Ex-vivo uterine environment (EVE) therapy uses an artificial placenta to provide gas exchange and nutrient delivery to a fetus submerged in an amniotic fluid bath. Development of EVE may allow us to treat very premature neonates without mechanical ventilation. Meanwhile, elevations in fetal inflammation are associated with adverse neonatal outcomes. In the present study, we analysed fetal survival, inflammation and pulmonary maturation in preterm lambs maintained on EVE therapy using a parallelised umbilical circuit system with a low priming volume.

Methods: Ewes underwent surgical delivery at 115 days of gestation (term is 150 days), and fetuses were transferred to EVE therapy (EVE group; n = 5). Physiological parameters were continuously monitored; fetal blood samples were intermittently obtained to assess wellbeing and targeted to reference range values for 2 days. Age-matched animals (Control group; n = 6) were surgically delivered at 117 days of gestation. Fetal blood and tissue samples were analysed and compared between the two groups.

Results: Fetal survival time in the EVE group was 27.0 ± 15.5 (group mean ± SD) hours. Only one fetus completed the pre-determined study period with optimal physiological parameters, while the other 4 animals demonstrated physiological deterioration or death prior to the pre-determined study end point. Significant elevations (p<0.05) in: i) inflammatory proteins in fetal plasma; ii) selected cytokine/chemokine mRNA expression levels in fetal tissues; and iii) histological inflammatory score in fetal lung, were observed in the EVE group compared to the Control group. There was no significant difference (p>0.05) in surfactant protein mRNA expression level between the two groups.

Conclusion: In this study, we achieved limited fetal survival using EVE therapy. Despite this, EVE therapy only induced a modest fetal inflammatory response and did not promote lung maturation. These data provide additional insight into markers of treatment efficacy for the assessment of future studies.

No MeSH data available.


Related in: MedlinePlus

Relative expression of inflammatory cytokine/chemokine mRNA levels in fetal circulating immunocytes measured with quantitative PCR.H: hours after induction of EVE therapy. Values of IL-1β, TNF-α, and MCP-2 are presented as bar charts with the group mean normalised expression vs. the value for Control group, with error bars representing SD. Values of IL-6 and IL-8 are presented as box plots with the group median normalised expression vs. the value for Control group, with whiskers representing maximum and minimum values. Significant difference vs. value for Control group is indicated: ‡, p<0.01; significant difference vs. value for 0 H group is indicated: ^, p<0.01.
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pone.0140701.g004: Relative expression of inflammatory cytokine/chemokine mRNA levels in fetal circulating immunocytes measured with quantitative PCR.H: hours after induction of EVE therapy. Values of IL-1β, TNF-α, and MCP-2 are presented as bar charts with the group mean normalised expression vs. the value for Control group, with error bars representing SD. Values of IL-6 and IL-8 are presented as box plots with the group median normalised expression vs. the value for Control group, with whiskers representing maximum and minimum values. Significant difference vs. value for Control group is indicated: ‡, p<0.01; significant difference vs. value for 0 H group is indicated: ^, p<0.01.

Mentions: Significant elevation in MCP-2 mRNA expression level in circulating immunocytes isolated from fetal arterial blood was detected at 12 hours after induction of EVE therapy compared to both the Control and the 0 hour point in the EVE group (Fig 4).


Ex-Vivo Uterine Environment (EVE) Therapy Induced Limited Fetal Inflammation in a Premature Lamb Model.

Miura Y, Saito M, Usuda H, Woodward E, Rittenschober-Böhm J, Kannan PS, Musk GC, Matsuda T, Newnham JP, Kemp MW - PLoS ONE (2015)

Relative expression of inflammatory cytokine/chemokine mRNA levels in fetal circulating immunocytes measured with quantitative PCR.H: hours after induction of EVE therapy. Values of IL-1β, TNF-α, and MCP-2 are presented as bar charts with the group mean normalised expression vs. the value for Control group, with error bars representing SD. Values of IL-6 and IL-8 are presented as box plots with the group median normalised expression vs. the value for Control group, with whiskers representing maximum and minimum values. Significant difference vs. value for Control group is indicated: ‡, p<0.01; significant difference vs. value for 0 H group is indicated: ^, p<0.01.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4608829&req=5

pone.0140701.g004: Relative expression of inflammatory cytokine/chemokine mRNA levels in fetal circulating immunocytes measured with quantitative PCR.H: hours after induction of EVE therapy. Values of IL-1β, TNF-α, and MCP-2 are presented as bar charts with the group mean normalised expression vs. the value for Control group, with error bars representing SD. Values of IL-6 and IL-8 are presented as box plots with the group median normalised expression vs. the value for Control group, with whiskers representing maximum and minimum values. Significant difference vs. value for Control group is indicated: ‡, p<0.01; significant difference vs. value for 0 H group is indicated: ^, p<0.01.
Mentions: Significant elevation in MCP-2 mRNA expression level in circulating immunocytes isolated from fetal arterial blood was detected at 12 hours after induction of EVE therapy compared to both the Control and the 0 hour point in the EVE group (Fig 4).

Bottom Line: Meanwhile, elevations in fetal inflammation are associated with adverse neonatal outcomes.There was no significant difference (p>0.05) in surfactant protein mRNA expression level between the two groups.Despite this, EVE therapy only induced a modest fetal inflammatory response and did not promote lung maturation.

View Article: PubMed Central - PubMed

Affiliation: School of Women's and Infants' Health, The University of Western Australia, Crawley, Western Australia, Australia; Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan.

ABSTRACT

Introduction: Ex-vivo uterine environment (EVE) therapy uses an artificial placenta to provide gas exchange and nutrient delivery to a fetus submerged in an amniotic fluid bath. Development of EVE may allow us to treat very premature neonates without mechanical ventilation. Meanwhile, elevations in fetal inflammation are associated with adverse neonatal outcomes. In the present study, we analysed fetal survival, inflammation and pulmonary maturation in preterm lambs maintained on EVE therapy using a parallelised umbilical circuit system with a low priming volume.

Methods: Ewes underwent surgical delivery at 115 days of gestation (term is 150 days), and fetuses were transferred to EVE therapy (EVE group; n = 5). Physiological parameters were continuously monitored; fetal blood samples were intermittently obtained to assess wellbeing and targeted to reference range values for 2 days. Age-matched animals (Control group; n = 6) were surgically delivered at 117 days of gestation. Fetal blood and tissue samples were analysed and compared between the two groups.

Results: Fetal survival time in the EVE group was 27.0 ± 15.5 (group mean ± SD) hours. Only one fetus completed the pre-determined study period with optimal physiological parameters, while the other 4 animals demonstrated physiological deterioration or death prior to the pre-determined study end point. Significant elevations (p<0.05) in: i) inflammatory proteins in fetal plasma; ii) selected cytokine/chemokine mRNA expression levels in fetal tissues; and iii) histological inflammatory score in fetal lung, were observed in the EVE group compared to the Control group. There was no significant difference (p>0.05) in surfactant protein mRNA expression level between the two groups.

Conclusion: In this study, we achieved limited fetal survival using EVE therapy. Despite this, EVE therapy only induced a modest fetal inflammatory response and did not promote lung maturation. These data provide additional insight into markers of treatment efficacy for the assessment of future studies.

No MeSH data available.


Related in: MedlinePlus