The Omentum as a Lymphoid Tissue: Its Molecular Aspects and Application in a Murine Model

Abstract The omentum is a vascularized, immune-active tissue with regenerative potential, particularly when activated by intraperitoneal stimuli. Its secreted factors may promote lymphangiogenesis, offering a novel approach to lymphedema treatment. The omentum was activated in mice using an intraperitoneal polydextran slurry. Gene expression was evaluated over time to assess inflammatory and lymphatic markers. Culture supernatants from the activated omentum were collected, and vascular endothelial growth factor-C (VEGF-C) levels were measured. Therapeutic potential was tested in a mouse hindlimb lymphedema model through local application of the supernatant. Histological analysis assessed skin thickness, lymphatic vessel density, and macrophage infiltration. Activation of the omentum induced early upregulation of hypoxia-inducible factor-1 α (HIF-1α) and angiopoietin-2 (Ang2), followed by increased expression of Forkhead Box C2 (Foxc2) and Prospero homeobox-1 (Prox1) by day 7, indicating lymphatic maturation. VEGF-C levels in the supernatant were significantly elevated. In the lymphedema model, treated mice exhibited reduced peak edema, faster resolution, and increased skin thickness and lymphatic vessel density compared with controls. Histological analysis revealed enhanced lymphangiogenesis and reduced macrophage infiltration. Downregulation of lymphatic vessel endothelial hyaluronan receptor 1 (Lyve1) and Neuropilin-1 (NRP1) suggested a predominance of tissue remodeling over structural maintenance. Activated omental tissue secretes potent bioactive factors that promote lymphangiogenesis and tissue regeneration. These findings indicate the potential of activated omentum for functional characterization and possible applications in regenerative medicine. Further investigation in chronic and clinical models is warranted to advance its translational potential.