Donor mesenchymal stem cell kinetics after transamniotic stem cell therapy (TRASCET) in a rodent model of gastroschisis.

Abstract

PURPOSE: We sought to comprehensively scrutinize donor mesenchymal stem cell kinetics following transamniotic stem cell therapy (TRASCET) in experimental gastroschisis. METHODS: A gastroschisis was surgically created in 102 rat fetuses at gestation day 18 (term&#x202f;=&#x202f;22&#x202f;days), immediately followed by volume-matched amniotic injections of either amniotic fluid mesenchymal stem cells (afMSCs) labeled with a luciferase reporter gene (n&#x202f;=&#x202f;58), or luciferase protein alone (n&#x202f;=&#x202f;44). Samples from multiple anatomical sites from survivors were screened for luciferase activity via microplate luminometry at term. Statistical analysis included Mann-Whitney U-test, Wald test, and kappa coefficient (p&#x202f;<&#x202f;0.05). RESULTS: Overall survival was 42% (43/102), with no significant difference between the two groups (p&#x202f;=&#x202f;0.82). When controlled by acellular luciferase, donor afMSCs were identified selectively in the placenta (p&#x202f;<&#x202f;0.001) and bowel (p&#x202f;=&#x202f;0.005), independently of the dams (respectively, p&#x202f;<&#x202f;0.001 and p&#x202f;=&#x202f;0.041). Bowel homing was documented exclusively in areas exposed to the amniotic cavity. There was no mutual correlation between placental and bowel homing (kappa&#x202f;=&#x202f;-0.02; p&#x202f;=&#x202f;0.91). CONCLUSIONS: Amniotic mesenchymal stem cells home to specific sites after TRASCET in the setting of gastroschisis. Placental homing and intestinal homing are central yet seemingly independent constituents of cell trafficking, suggesting that both direct amniotic seeding and hematogenous routing take place. LEVEL OF EVIDENCE: N/A (animal and laboratory study).