Anti-inflammatory effects of antenatal administration of stem cell derived extracellular vesicles in the brain of rat fetuses with congenital diaphragmatic hernia

Blundell, Matisse; Doktor, Fabian; Figueira, Rebeca L.; Khalaj, Kasra; Biouss, George; Antounians, Lina; Zani, Augusto

doi:10.1007/s00383-023-05578-9

Cited by 6 publications

(1 citation statement)

References 58 publications

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“…89 Interestingly, localization of AFSC-EVs in the fetal brain of rats with CDH was associated with reduced brain tissue inflammation, evidenced by a decreased activation of microglia. 90 Lastly, testing administration of GMP-grade AFSC-EVs in a large animal model of oligohydramnios, such as the fetal lamb model, will allow us to test their pharmacokinetic and pharmacodynamic properties, as well as the safety for the mother, as EVs are able to cross the placental barrier. 91 Increasing clinical usage of EVs together with our experimental data warrant further investigations on stem cell derived EVs as a potential novel regenerative therapy.…”

Section: Afsc-ev Administration Restores the Tgf-β Signaling Pathway ...mentioning

confidence: 99%

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

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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.

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Section: Afsc-ev Administration Restores the Tgf-β Signaling Pathway ...mentioning

confidence: 99%

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

show abstract

Sex-specific differences in the severity of pulmonary hypoplasia in experimental congenital diaphragmatic hernia and implications for extracellular vesicle-based therapy

Doktor,

Lo,

Fortuna

et al. 2024

Pediatr Surg Int

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Antenatal Administration of Extracellular Vesicles Derived From Amniotic Fluid Stem Cells Improves Lung Function in Neonatal Rats With Congenital Diaphragmatic Hernia

Figueira,

Khoshgoo,

Doktor

et al. 2024

Journal of Pediatric Surgery

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Anti-inflammatory effects of antenatal administration of stem cell derived extracellular vesicles in the brain of rat fetuses with congenital diaphragmatic hernia

Cited by 6 publications

References 58 publications

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

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

Sex-specific differences in the severity of pulmonary hypoplasia in experimental congenital diaphragmatic hernia and implications for extracellular vesicle-based therapy

Antenatal Administration of Extracellular Vesicles Derived From Amniotic Fluid Stem Cells Improves Lung Function in Neonatal Rats With Congenital Diaphragmatic Hernia

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