141 - Placental Small Extracellular Vesicles (sEVs) reduce pro-inflammatory cytokines production in Lipopolysaccharide (LPS) Induced Lung Injury

Poster Number: 141
Publication Number: 141.436

Ranga Prasanth Thiruvenkataramani, Michigan State University College of Human Medicine, Lansing, MI, United States; Amal Abdul-Hafez, Michigan State University College of Human Medicine, East Lansing, MI, United States; Hend Mohamed, Pediatrics and Human development, MSU, Lansing, MI, United States; Sherif Abdelfattah, Michigan State University, East Lansing, MI, United States; Hattan Arif, Michigan State University College of Human Medicine, Haslett, MI, United States; Myrna Y. Gonzalez Arellano, Michigan State University College of Human Medicine, Lansing, MI, United States; Mohammed Abdulmageed, Michigan State University College of Human Medicine/Sparrow Hospital Regional Neonatal Intensive Care Unit, East Lansing, MI, United States; Tarek Mohamed, Michigan State University College of Human Medicine, East Lansing, MI, United States; Burra V. Madhukar, Michigan State University, E. Lansing, MI, United States; Said Omar, Michigan State University College of Human Medicine, Lansing, MI, United States

Background: In neonates, sepsis-induced acute lung injury secondary to chorioamnionitis or pneumonia is a risk factor for increasing morbidity and mortality and Bronchopulmonary Dysplasia (BPD). Stem cell therapy was shown to alleviate acute lung injury. Mesenchymal stem cells (MSCs) derived Extracellular vesicles (EVs) play a critical role in the immune system modulation and tissue regeneration. EVs are classified based on their size as small and large EVs, or biogenesis as apoptotic bodies, microvesicles, and exosomes. We previously showed that Wharton jelly (WJ) and placental (PL) MSCs conditioned culture media containing small EV (sEVs)  prevent the cytotoxic effects of lipopolysaccharide (LPS) on lung alveolar epithelial cells. In this study, we investigate the immunomodulatory mechanism of placental sEVs in acute lung injury due to infection 

Objective: To determine the effects of WJ- and PL-MSCs-derived sEVs on the release of proinflammatory cytokines from alveolar epithelial cells after LPS treatment

Design/Methods: Placentas were collected from healthy full-term pregnancies after obtaining maternal consent. Pl- and WJ- MSCs were isolated and cultured for the collection of sEVs from  the conditioned media by ultrafiltration. Particle-size distribution was performed by nanoparticle tracking analysis (NTA). Size and morphology of the isolated sEVs were confirmed by transmission electron microscopy (TEM). The presence of the  sEVs surface markers was checked by western blotting. Cultured alveolar epithelial A549 cells were incubated 24hr +/- placental sEVs then 24hr +/- LPS. Supernatant media was collected, and Interleukin (IL)-6 and IL-8 cytokines were measured by ELISA technique

Results: NTA, TEM, and western blotting confirmed size distribution, morphology, and presence of sEVs surface markers in the isolated WJ- and PL- sEVs (Fig.1). LPS-treated cells showed a significant increase in secreted IL-6 and IL-8. The treatment with WJ- and PL- sEVs caused a similar multifold decrease in the LPS-induced release of both IL-6 and IL-8 compared with the corresponding controls (Fig.2) 

Conclusion(s): Placental and Wharton Jelly-derived sEVs decrease the release of pro-inflammatory cytokines from alveolar epithelial cells in response to LPS treatment. This suggests placental sEVs can modulate the immune response and decrease lung inflammation in sepsis and represent a promising therapeutic option for the prevention of sepsis-induced lung injury and the development of BPD in neonates