Poster W19 - Alginate Encapsulated Cells for Local Delivery of Immunomodulatory Cytokines in Acute Respiratory Distress Syndrome

Introduction: Acute Respiratory Distress Syndrome (ARDS) is a severe lung disease characterized by widespread inflammation and tissue damage, resulting in impaired breathing and oxygenation. Conventional treatments, including mechanical ventilation and systemic administration of anti-inflammatory agents, exhibit limited efficacy and significant adverse effects. Encapsulated cells present a novel approach for targeted delivery of anti-inflammatory cytokines to the lung tissue in ARDS.

Materials and

Methods: Here, retinal pigment epithelial cells were genetically modified using a piggyback transposon-mediated cell engineering approach, to produce anti-inflammatory cytokines, interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL-1Ra). These cells were subsequently encapsulated within the biocompatible polymer, alginate, generating capsules of approximately 300um in diameter. The encapsulated cells were then directly delivered to the bronchoalveolar space in a lipopolysaccharide-induced ARDS rat model. We extensively evaluated both the pharmacokinetics and dynamics of our drug delivery approach via ELISA. To validate therapeutic efficacy the presence of inflammatory cytokines in the BAL was evaluated post-treatment, and lungs were sectioned and stained to assess the degree of immune infiltration. H&E stained lung sections were additionally scored in MatLab to blindedly assess the extent of injury- ranging from normal, to severe.

Results, Conclusions, and Discussions: Our findings reveal a sustained gradient of cytokine concentration in the local area compared to systemic levels over seven days, significantly reducing the need for frequent exogenous cytokine administration. Treatment with our cytokine platform markedly decreased several pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, including IL-1α, TNF-α, and CCL2, compared to control groups. This effect was observed as early as 12 hours post-treatment, demonstrating the efficiency of this approach in improving outcomes. Lung injury scores mirrored the reduced inflammation, showing significant reductions in immune cell infiltration. Additionally, the kinetics of this response indicated sustained improvement compared to controls at 1, 3, 7, 14, and 21 days post-treatment. Overall, our results underscore the potential of a localized system for immunomodulation in the treatment of acute respiratory distress syndrome (ARDS).

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