Abstract
Using a mouse model of intrauterine inflammation, we have demonstrated that exposure to inflammation induces preterm birth and perinatal brain injury. Mesenchymal stem cells (MSCs) have been shown to exhibit immunomodulatory effects in many inflammatory conditions. We hypothesized that treatment with human adipose tissue-derived MSCs may decrease the rate of preterm birth and perinatal brain injury through changes in antiinflammatory and regulatory milieu.
A mouse model of intrauterine inflammation was used with the following groups: (1) control; (2) intrauterine inflammation (lipopolysaccharide); and (3) intrauterine lipopolysaccharide + intraperitoneal (MSCs). Preterm birth was investigated. Luminex multiplex enzyme-linked immunosorbent assays were performed for protein levels of cytokines in maternal and fetal compartments. Immunofluorescent staining was used to identify and localize MSCs and to examine microglial morphologic condition and neurotoxicity in perinatal brain. Behavioral testing was performed at postnatal day 5.
Pretreatment with MSCs significantly decreased the rate of preterm birth by 21% compared with the lipopolysaccharide group (P < .01). Pretreatment was associated with increased interleukin-10 in maternal serum, increased interleukin-4 in placenta, decreased interleukin-6 in fetal brain (P < .05), decreased microglial activation (P < .05), and decreased fetal neurotoxicity (P < .05). These findings were associated with improved neurobehavioral testing at postnatal day 5 (P < .05). Injected MSCs were localized to placenta.
Maternally administered MSCs appear to modulate maternal and fetal immune response to intrauterine inflammation in the model and decrease preterm birth, perinatal brain injury, and motor deficits in offspring mice.