INTRAVASCULAR INFUSIBLE EXTRA CELLULAR MATRIX MODULATES INFLAMMATORY RESPONSE IN MOUSE MODEL OF SYSTEMIC INFLAMMATION

ABSTRACT

Introduction: Systemic inflammatory conditions (e.g. sepsis and severe viral infections like COVID-19) are characterized by an overwhelming innate immune response that leads to multi-organ failure [1]. Decellularized extra cellular matrices (ECM) have previously demonstrated pro-regenerative properties through modulation of the immune response [2]. Infusible ECM (iECM) was developed for systemic delivery, targeting and treating sites of vascular injury. We hypothesized iECM delivery would dampen the systemic inflammatory response in a lipopolysaccharide (LPS) mouse model. Methods: iECM was prepared from decellularized porcine left ventricle based on previous protocols [3]. C57BL6/J mice underwent dual intraperitoneal LPS injection and then tail vein injection of saline or iECM (10 mg/mL). Thirty hours post-LPS dose, mice were euthanized and heart, lungs, brain, kidneys, spleen, and liver were harvested (n = 6 mice/group). Tissues were processed for gene expression by qRT-PCR and Nanostring nCounter® Immunology Panels, immune cell identification by flow cytometry, and cytokines by Legend Plex® Mouse Inflammation Panels. Results: qRT-PCR identified significant downregulation of Il1b and Il6 across multiple tissue types in iECM vs. saline-treated mice. Nanostring transcriptomic analysis confirmed downregulation of multiple inflammatory cytokines and chemokines. IL-6 cytokine expression was significantly reduced across multiple organs along with IL-1α and IFN-γ in the lungs, and IL-1β and IL-17A in the spleen. Discussion: Results demonstrated iECM dampens the systemic inflammatory response to LPS, indicating its potential for treating conditions such as sepsis and COVID-19 pathology.