Fetal bone marrow homing of donor mesenchymal stem cells after transamniotic stem cell therapy (TRASCET)

Abstract

PurposeDonor cell engraftment patterns following transamniotic stem cell therapy (TRASCET) with amniotic fluid mesenchymal stem cells (afMSCs) are incompatible with solely direct amniotic seeding. We sought to determine whether fetal bone marrow is a component of such engraftment and to examine the chronology of afMSC placental trafficking. MethodsTwo groups of Sprague–Dawley rat fetuses received volume-matched intraamniotic injections on gestational day 17 (E17; term E22): either afMSCs labeled with a luciferase reporter gene or luciferase protein alone. Placental samples were procured at daily time points thereafter until term. Fetal bone marrow was obtained at term only owing to size constraints. Specimens were screened for luminescence via microplate luminometry. ResultsDonor afMSCs were identified in the bone marrow and placenta of fetuses receiving labeled afMSCs, but not in those receiving luciferase alone (P<0.001). Luminescence was significantly higher in placentas at E18 compared to E19 (P<0.001), E20 (P=0.007), and E21 (P=0.004), with no difference with E22/term (P=0.97). ConclusionsDonor mesenchymal stem cells home to the fetal bone marrow after intraamniotic injection. The chronology of placental trafficking is suggestive of controlled cell routing rather than plain cell clearance. Fetal bone marrow engraftment of donor cells significantly expands potential applications of transamniotic stem cell therapy.