Adipogenic MSC-derived COL-3 Drives M2 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 and promoted macrophage polarization toward the anti-inflammatory M2 phenotype via the PI3K-AKT signaling pathway. In a mouse model of sepsis-induced lung injury, treatment with lyophilized extracellular matrix from adipogenic adipose-derived stem cells alleviated lung inflammation and injury, accompanied by increased infiltration of M2 macrophages. These results identify a novel mechanism by which stem cell-derived type III collagen modulates the immune microenvironment and suggest a new therapeutic approach for inflammatory lung diseases.