Figure 1.

Lymphatic neovascularization mediated by BM-derived POD⁺CD11b⁺ cells. Pathophysiologic conditions such as tumors or wounds can induce generation and mobilization of POD⁺CD11b⁺ (POD⁺) LEPCs from BM to circulation, via growth factors or cytokines, including VEGFA and VEGFC. Although the mechanisms by which BM-MNCs or HSCs become POD⁺CD11b⁺ LEPCs need further investigation, the selective expression of POD in CD11b⁺ myelomonocytes in response to environmental cues can confer CD11b⁺ cells to express stem/progenitor cell characteristics. Alternatively, POD⁺CD11b⁺ cells in BM can be exclusively expanded in response to the above stimuli. The mobilized POD⁺CD11b⁺ LEPCs migrate to peripheral tissues and contribute to new lymphatic vessel formation through lymphvasculogenesis (i.e. LEPCs become LECs) and lymphangiogenesis (i.e. LEPCs provide lymphangiogenic factors to enhance proliferation of pre-existing LECs). POD; PODOPLANIN, HSCs; hematopoietic stem cells, BM-MNCs; bone marrow mononuclear cells