Anna L. David

Objective To investigate the maternal and fetal safety of In utero stem cell transplantation (IUSCT). Methods Medline®, Embase and Cochrane library (1967−2023) search for publications reporting IUSCT in humans. Two reviewers independently screened abstracts and full‐text papers. Results Sixty six transplantation procedures in 52 fetuses were performed for haemoglobinopathies ( n = 14), red cell/bleeding disorders ( n = 4), immunodeficiencies ( n = 15), storage disorders ( n = 7), osteogenesis imperfecta ( n = 2) and healthy fetuses ( n = 10). The average gestational age was 18.9 weeks; of procedures reporting the injection route, cells were delivered by intraperitoneal ( n = 37), intravenous ( n = 19), or intracardiac ( n = 4) injection or a combination ( n = 3); most fetuses received one injection ( n = 41). Haematopoietic ( n = 40) or mesenchymal ( n = 12) stem cells were delivered. The cell dose was inconsistently reported (range 1.8−3.3 × 10 9 cells total ( n = 27); 2.7−5.0 × 10 9 /kg estimated fetal weight ( n = 17)). The acute fetal procedural complication rate was 4.5% (3/66); the acute fetal mortality rate was 3.0% (2/66). Neonatal survival was 69.2% (36/52). Immediate maternal and pregnancy outcomes were reported in only 30.8% (16/52) and 44.2% (23/52) of cases respectively. Four fetal/pregnancy outcomes would also classify as ≥ Grade 2 maternal adverse events. Conclusions Short‐, medium‐, and long‐term maternal and fetal adverse events should be reported in all IUSCT studies.

Objective The effects of mechanical stimulation in preterm amniotic membrane (AM) defects were explored. Methods Preterm AM was collected from women undergoing planned preterm caesarean section (CS) due to fetal growth restriction or emergency CS after spontaneous preterm prelabour rupture of the membranes (sPPROM). AM explants near the cervix or placenta were subjected to trauma and/or mechanical stimulation with the Cx43 antisense. Markers for nuclear morphology (DAPI), myofibroblasts (αSMA), migration (Cx43), inflammation (PGE 2 ) and repair (collagen, elastin and transforming growth factor β [TGFβ 1 ]) were examined by confocal microscopy, second harmonic generation, qPCR and biochemical assays. Results In preterm AM defects, myofibroblast nuclei were highly deformed and contractile and expressed αSMA and Cx43. Mechanical stimulation increased collagen fibre polarisation and the effects on matrix markers were dependent on tissue region, disease state, gestational age and the number of fetuses. PGE 2 levels were broadly similar but reduced after co‐treatment with Cx43 antisense in late sPPROM AM defects. TGFβ 1 and Cx43 gene expression were significantly increased after trauma and mechanical stimulation but this response dependent on gestational age. Conclusion Mechanical stimulation affects Cx43 signalling and cell/collagen mechanics in preterm AM defects. Establishing how Cx43 regulates mechanosignalling could be an approach to repair tissue integrity after trauma.