Adipogenic MSC-derived COL-3 drives M2-like macrophage polarization via PI3K-AKT to alleviate sepsis-induced lung injury

Sepsis-induced acute lung injury is a critical condition marked by uncontrolled inflammation and immune imbalance. Here, we investigated the role of extracellular matrix components derived from adipogenically differentiated adipose-derived stem cells in regulating macrophage polarization and lung injury. We found that type III collagen was significantly upregulated in the extracellular matrix after adipogenic induction. Treatment with COL-3 alone enhanced M2-like phenotypic features in macrophages, and pharmacological intervention results supported the involvement of AKT signaling in COL-3-associated responses. In a mouse model of sepsis-induced lung injury, treatment with lyophilized extracellular matrix from adipogenically differentiated adipose-derived stem cells alleviated lung inflammation and injury, accompanied by increased infiltration of M2-like macrophages. These results support a role for stem cell-derived type III collagen in regulating the immune microenvironment and suggest a new therapeutic approach for inflammatory lung diseases.