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Basic Science

Poster Session 1

(306) A Multi-Organ-on-Chip Model to Study the Efficacy of Exosomal Therapeutics in Treating Inflammation-Associated Adverse Pregnancies

Tuesday, February 13, 2024
10:30 AM – 12:00 PM  
Location: Prince George's Exhibit Hall CDE, Lower Atrium Level
Objective: Infection and inflammation are two major risk factors for preterm birth. There is a lack of physiologically-relevant human models of the two feto-maternal interfaces (FMi; placenta and fetal membranes with decidua) to test anti-inflammatory drug efficacy and functions in an in vitro setting. We used a fetal membrane-placenta organ-on-chip (FMi-PLA-OOC) to mimic infectious inflammation of the FMi and conduct pre-clinical drug testing (cytotoxicity, mechanism of action, and efficacy) using a novel anti-inflammatory compound, exosomal-derived interleukin-10 (eIL-10), engineered to facilitate drug passage across FMi barriers.

Study Design: FMi-PLA-OOC contained cells from human umbilical cord endothelium, cyto- and syncytiotrophoblasts, decidua, chorion, and amnion (mesenchyme and epithelium) in seven cell chambers connected through collagen-filled microchannels. The decidual cells were treated with lipopolysaccharide (LPS; 100ng/mL) followed by a co-treatment of LPS and eIL-10 (500ng/mL) (Fig 1A). LPS and eIL-10 propagation and P-NF-kB expression were determined by immunostaining, functional IL-10 signaling (Quant blue assay), and inflammation (multiplex cytokine assay).

Results: Maternal-to-fetal propagation of LPS occurred within 6 days without inducing cytotoxicity of cells in the FMi-PLA-OOC (Fig 1B-C). LPS induced P-NF-kB expression (Fig 1D) and induced pro-inflammatory cytokines (IL-6, IL-8, TNF-a) across the fetal membrane and placenta layers (Fig 1E; [black *-p< 0.05 normalized to control]). eIL-10 did not induce cytotoxicity (Fig 1B) within the maternal or fetal cells and propagated to distal chambers within 3 days (Fig 1C). LPS+eIL-10 co-treatment induced IL-10 signaling pathways (Fig 1F), reduced P-NF-kB expression (Fig 1D), and suppressed LPS-induced pro-inflammatory cytokine production in the fetal membranes and placenta (red *-p< 0.05 normalized to LPS) (Fig 1E).

Conclusion: Using this model, we successfully tested the ability of eIL-10 to suppress LPS-induced inflammation at the FMi. FMi-PLA-OOC is an alternative to animal models for preclinical testing of drugs during pregnancy.