Nanoparticle mediated increased insulin-like growth factor 1 expression enhances human placenta syncytium function

Area of Science:

• Obstetrics and Gynecology
• Nanomedicine
• Placental Biology

Background:

• Placental dysfunction underlies major obstetric diseases, with limited treatment options for complications like fetal growth restriction (FGR).
• Previous studies showed nanoparticle delivery of human insulin-like growth factor 1 (hIGF1) transgene maintained fetal growth in a mouse model of FGR.
• Uptake by human placental syncytiotrophoblast remained to be determined.

Purpose of the Study:

• To determine nanoparticle uptake by human placental syncytiotrophoblast.
• To assess nanoparticle-mediated transgene expression and functional responses in human placental models.
• To evaluate the protective effects of nanoparticle delivery against oxidative stress.

Main Methods:

• Utilized an ex vivo human placenta perfusion model and term placenta villous fragments.
• Employed in vitro syncytiotrophoblast models (BeWo cells, primary trophoblasts).
• Quantified nanoparticle uptake via fluorescence, transgene expression (hIGF1), and functional responses including glucose transporter 1 translocation and cell viability under oxidative stress.

Main Results:

• Confirmed nanoparticle uptake in human placental syncytiotrophoblasts using ex vivo perfusion and histology.
• Demonstrated significant increases in hIGF1 transgene expression across various human placental models.
• Observed functional improvements, including glucose transporter 1 translocation and protection against oxidative stress-induced cell death and mitochondrial dysfunction.

Conclusions:

• The study confirms successful nanoparticle uptake by the human placental syncytium.
• Nanoparticle delivery leads to enhanced transgene expression and significant functional improvements in placental cells.
• These findings support the potential of this nanoparticle system for therapeutic applications in obstetric complications like FGR.