Transamniotic Delivery of Hematopoietic Stem Cells Genetically Modified to Carry a Human Hemoglobin Subunit Beta Gene (HBB) in a Healthy Rodent Model.

Background: We sought to determine whether transamniotic stem cell therapy (TRASCET) could be a viable alternative for the fetal administration of genetically modified hematopoietic stem cells (HSCs) carrying a human hemoglobin subunit beta gene (hHBB) in a healthy syngeneic rat model.

Methods: Time-dated pregnant Lewis dams underwent volume-matched intra-amniotic injections in all their fetuses (n = 61) of a suspension of donor HSCs genetically modified with either both a hHBB gene and a firefly luciferase reporter gene (n = 42) or the firefly luciferase reporter gene alone to control for HBB-derived protein interspecies homology (n = 19) on gestational day 17 (E17; term = E21). Donor HSCs consisted of syngeneic cells phenotyped by flow cytometry with successful hHBB transduction confirmed by ELISA prior to administration in vivo.

Perinatal Vaccination by Transamniotic Fetal mRNA Delivery: Immunization Against Human Cytomegalovirus in a Rodent Model.

Purpose: Gestational cytomegalovirus (CMV) infection is a prevalent disease with significant fetal and neonatal morbidity. MRNA vaccines have emerged as powerful options for postnatal immunization against infections. It has been shown that mRNA delivered into the amniotic fluid reaches the fetal circulation via the placenta.

Transamniotic Delivery of Surfactant Protein B mRNA in a Healthy Model.

Introduction: We sought to determine whether exogenous surfactant protein B (SPB) mRNA could be incorporated and translated by the fetal lung after simple transamniotic administration.

Methods: Fetuses (n = 149) of twelve time-dated dams underwent intra-amniotic injections of either human SPB (hSPB) mRNA encapsulated into lipopolyplex (mRNA, n = 99) or lipopolyplex without mRNA (control; n = 50) on gestational day 17 (E17, term = E21-22). Lungs were screened for hSPB by enzyme-linked immunosorbent assay daily until term.

Comparative Effects on Fetal Hematopoiesis and Placental Inflammation From Mesenchymal and Hematopoietic Stem Cells as Agents of Transamniotic Stem Cell Therapy (TRASCET) in a Syngeneic Model of Intrauterine Growth Restriction.

Purpose: We compared transamniotic stem cell therapy (TRASCET) using either mesenchymal (MSCs) or hematopoietic (HSCs) stem cells on fetal hematopoiesis in a syngeneic model of intrauterine growth restriction (IUGR).

Methods: Lewis dams exposed to cycling hypoxia (10.5% O) in late gestation had their fetuses (n = 83) either receiving no intervention (untreated; n = 9), or intra-amniotic injections of either HSCs (HSC; n = 34), MSCs primed to an enhanced anti-inflammatory phenotype (primed-MSC; n = 28), or saline (sham; n = 12).