A model for lymphatic regeneration in tissue repair of the intestinal muscle coat.

The gastrointestinal lymphatic system, which comprises a network of thin-walled vessels, is essential for the regulation of tissue fluid volume, immune function, and transport of fatty nutrients. The identification of specific lymphatic endothelial markers has facilitated analyses of lymphatic organization and lymphangiogenesis during individual development and tissue repair. The intestinal muscle coat producing motor activity develops a dense maze-like lymphatic network by vascular sprouting consisting of thin lymphatic endothelial projections and splitting of the vessels. The lymphatic regeneration in the tissue repair of the intestinal muscle coat is essentially attributable to sprouting from preexisting lymphatics, and it progresses vigorously with vascular maturation. The regrowing lymphatic endothelial cells exhibit structural changes indicating a high migratory potential and a close association with regenerating stromal cells. The upregulation of VEGF-C, a specific lymphangiogenic molecule, in a subpopulation of the stromal cells probably contributes to lymphatic regeneration by activating its receptor, VEGFR-3, on the regrowing lymphatic endothelial cells.