Mesenchymal stem cells ameliorate intra-amniotic inflammation-related neonatal complications in rats

Abstract

Objective: The aim of this study was to establish a novel rat model of neonatal complications secondary to intra-amniotic infection/inflammation in order to investigate the therapeutic efficacy of rat umbilical cord-derived mesenchymal stem cells (rUCMSCs).
Methods: On gestational age day (GAD) 16, approximately 0.2 μg of lipopolysaccharide (LPS) was directly injected into the amniotic cavity of a pregnant rat. Placental inflammation on GAD 20 was histologically evaluated and the cytokine (Il-1β, Tnfα, Mcp-1, Il-6, Cxcl-1) and prostaglandin synthesis enzyme (Cox-1, Cox-2) expression patterns were analyzed by quantitative real-time polymerase chain reaction. Neonatal lung and brain injuries on postnatal day (PND) 14 were assessed histologically. rUCMSCs were injected intravenously into pups to investigate their therapeutic efficacy.
Results: LPS significantly decreased alive-birth rates. Significant increases in inflammatory cell infiltration and up-regulation of Mcp-1 and Cox-2 expression were observed in the placenta. In the neonates, the areas staining positive for myelin basic protein in the brain and radial alveolar counts in the lungs were significantly reduced in the LPS group compared with the control group. rUCMSCs improved myelination and alveolarization.
Conclusion: Intrauterine injection of LPS causes placental inflammation along with neonatal brain and lung injuries in neonatal rats. Postnatal administration of rUCMSCs alleviates these neonatal complications.