Trans-Amniotic Stem Cell Therapy (TRASCET) in a Leporine Model of Gastroschisis

Abstract Background/Purpose Trans-amniotic stem cell therapy (TRASCET) with amniotic mesenchymal stem cells (afMSCs) has been shown to mitigate bowel damage in a rodent model of gastroschisis. As a pre-requisite to clinical translation, we sought to study TRASCET in a larger animal model. Methods New Zealand rabbit fetuses (n = 64) with surgically created gastroschisis were divided into three groups. One group (untreated) had no further manipulations. Two groups received volume-matched intra-amniotic injections of either saline or a suspension of afMSCs. Non-manipulated fetuses served as controls. Histomorphologic measurements of intestinal damage, along with biochemical profiling of inflammation markers, were performed at term. Statistical comparisons were by Fisher's exact test, ANOVA and the Wald test (P < 0.05). Results Overall survival was 62.5%. Segmental and total intestinal wall thicknesses were significantly decreased in the afMSC group compared with the untreated and saline groups (all P < 0.001), with no significant differences between untreated and saline groups (P = 0.24 to 1.00, depending on layer). Muscularis and serosal layers were significantly thicker in the afMSC group than in normal controls (P = 0.045 and P < 0.001, respectively). Conclusions Concentrated intra-amniotic injection of afMSC lessens, yet does not prevent, intestinal damage in a leporine model of gastroschisis. TRASCET may become a valuable strategy in the management of gastroschisis.