Bidirectional Feto-Maternal Traffic of Donor Mesenchymal Stem Cells Following Transamniotic Stem Cell Therapy (TRASCET).

ABSTRACT

PURPOSE: Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) has emerged experimentally as a potential treatment for different congenital diseases and maternal diseases of pregnancy. The broad applicability of TRASCET is predicated on hematogenous routing of donor MSCs via the placenta. We investigated whether donor MSC kinetics includes bidirectional traffic between the fetus and mother. METHODS: Eight time-dated dams had their fetuses (n = 96) divided in 4 groups on gestational day 17 (E17, term = E21). Groups populating one uterine horn received intra-amniotic injections (50 µL) of either donor amniotic fluid-derived MSCs (2×106 cells/mL) labelled with a firefly luciferase reporter gene (MSC-injected, n = 32), or of acellular luciferase (luciferase-injected, n = 26). Contra-lateral (CL) horn fetuses received no injection (MSC-CL, n = 20 and luciferase-CL, n = 18). At term, samples from 11 fetal anatomical sites from CL fetuses, along with placentas from all fetuses and maternal blood were screened for luciferase activity via microplate luminometry. RESULTS: Overall survival was 95 % (91/96). When controlled by the acellular injection, positive luciferase activity was observed in the placentas of all MSC-injected fetuses, confirming viability of the donor cells at term. When controlled by the acellular injection group, MSC-CL fetuses showed positive luciferase activity in the bone marrow, peripheral blood, brain and skin (p = <0.001-0.048). No luciferase activity was detected in any maternal blood sample. CONCLUSION: Amniotic fluid-derived MSCs can traffic between the fetus and mother in both directions after simple intra-amniotic injection, in a healthy rat model. This phenomenon must be considered in TRASCET performed in twin/multiple pregnancies. LEVEL OF EVIDENCE N/A (animal and laboratory study).