Characterization of the congenital diaphragmatic hernia model in C57BL/6J fetal mice: a step toward lineage tracing experiments

Doktor, Fabian; Figueira, Rebeca Lopes; Khalaj, Kasra; Ijaz, Aizah; Lacher, Martin; Blundell, Matisse; Antounians, Lina; Zani, Augusto

doi:10.1007/s00383-023-05583-y

Cited by 4 publications

(1 citation statement)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This picture of pulmonary hypoplasia is in line with that previously reported by others using the same model of oligohydramnios, 51 as well as by us in the CDH pulmonary hypoplasia model. 13,33,54 Treatment with AFSC-EVs improved lung growth as demonstrated by a higher fetal airspace density and rescued expression of Fgf10, Nrp1, and Ctnnb1 back to control level (Fig. 2D-E).…”

Section: Resultsmentioning

confidence: 90%

Amniotic fluid stem cell extracellular vesicles promote lung development via TGF-beta modulation in a fetal rat model of oligohydramnios

Doktor,

Figueira,

Fortuna

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Oligohydramnios (decreased amniotic fluid volume for gestational age) is a severe condition associated with high morbidity and mortality mainly due to fetal pulmonary hypoplasia. Currently, there are limited treatment options to promote fetal lung development. Administration of stem cells and their derivates have shown promising regenerative properties for several fetal and neonatal diseases related to arrested lung development. Herein, we first characterized pulmonary hypoplasia secondary to oligohydramnios in a surgical rat model. Experimental induction of oligohydramnios led to impaired lung growth, branching morphogenesis (fewer airspaces with decreasedFgf10,Nrp1,Ctnnb1expression), proximal/distal progenitor cell patterning (decreased Sox2 and Sox9 expression), and TGF-β signaling. We then tested antenatal administration of extracellular vesicles derived from amniotic fluid stem cells (AFSC- EVs). In oligohydramnios lungs, AFSC-EV administration improved lung branching morphogenesis and airway progenitor cell patterning at least in part through the release of miR-93-5p. Our experiments suggest that AFSC-EV miR-93-5p blocked SMAD 7, resulting in upregulation of pSMAD2/3 and restoration of TGF-β signaling. Conversely, oligohydramnios lungs treated with antagomir 93-5p transfected AFSC- EVs had decreased branching morphogenesis and TGF-β signaling. This is the first study reporting that antenatal administration of stem cell derivatives could be a potential therapy to rescue lung development in fetuses with oligohydramnios.HighlightsPulmonary hypoplasia secondary to oligohydramnios in fetal rats is characterized by impaired TGF-β signaling.AFSC-EV administration improves fetal lung branching morphogenesis and airway progenitor cell patterning.AFSC-EV effects are mediated at least in part via modulation of TGF-β signaling by the release of miR-93-5p from AFSC-EVs.

show abstract