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Neonatal Pulmonology

Neonatal Pulmonology 4: Exosomes, Stem Cells, Maternal and Fetal Environmental Effects

140 - Perinatal Electronic-Cigarette Exposure Induces Myogenic Differentiation of Bone Marrow-derived Mesenchymal Stem Cells

Monday, May 1, 2023

9:30 AM – 11:30 AM ET

Poster Number: 140
Publication Number: 140.436

Celia Yu, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States; Jie Liu, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States; Reiko Sakurai, The Lundquist Institute of Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States; Virender K.. Rehan, Harbor-UCLA Medical Center, Torrance, CA, United States

Presenting Author(s)

Celia Yu (she/her/hers)

Research Associate
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, United States

Background: Perinatal smoke exposure results in increased proclivity to chronic lung disease (CLD) in the exposed offspring; however, the underlying molecular mechanisms remain incompletely understood. We previously demonstrated that nicotine, which is a key contributor to smoke-induced lung damage, in addition to its direct effects on the developing lung also adversely affects the bone marrow-derived mesenchymal stem cells (BMSCs), a key player in lung injury and repair. Whether perinatal nicotine exposure in aerosolized form, i.e., via e-cigarette (e-cig) vaping also leads to similar effects is unknown. This is highly relevant due to the recent enormous increase in e-cig vaping by pregnant women.

Objective: To test the hypothesis that perinatal nicotine exposure via e-cig vaping alters molecular and phenotypic characteristics of BMSCs, predisposing them to a pro-myofibroblastic phenotype.

Design/Methods: Using an established e-cig delivery system, pair-fed pregnant rat dams received fresh air, vehicle (e-cig without nicotine), or e-cig (e-cig with nicotine) daily from embryonic day 6 until postnatal day (PND) 21 (N=3). Puffing topography [4s puffs, puff volume 35 ml every 30s at 30-min intervals, 12h/day, and 7 days/week] mimicked real-life topography. Pups delivered spontaneously at term and breastfed ad-lib but were not directly exposed to e-cig aerosols at any time. At PND21, pups were sacrificed and BMSCs were isolated. Cell proliferation, migration, wound healing response, and the expression of key Wnt and PPARγ signaling intermediates (PPARγ, C-EBPα) and myogenic markers (α-SMA, calponin, fibronectin) were determined by immunoblotting and qRT-PCR.

Results: The average maternal plasma nicotine level (7±4 ng/ml) during gestation with the vaping regimen used was within the range observed in pregnant women smoking 5-6 tobacco cigarettes/day. Compared to controls, perinatal e-cig exposure resulted in significant decreases in cell proliferation, migration, and wound healing capacity of the BMSCs (p< 0.05 for all). The expression and protein levels of key Wnt signaling intermediates (β-catenin, LEF-1) and myogenic proteins (α-SMA, calponin, fibronectin) increased significantly, while those of PPARγ and C-EBPα decreased significantly (p< 0.05 for all).

Conclusion(s): Perinatally e-cig exposed BMSCs demonstrated a pro-myofibroblastic phenotype and an impaired injury-repair potential, indicating a potentially similar susceptibility to CLD that is observed following perinatal nicotine exposure via tobacco smoking.