Potential Mechanisms of Interior Lymphatic Vessel Primo Vessels in Tissue Repair

The Primo Vascular System was discovered by Bong Han Kim in the 1960s when searching for an anatomical correlate of the acupuncture meridians used in eastern medicine. The Primo Vascular System is a systemic network of thread-like Primo-vessels with intermittent enlargements known as Primo-nodes. Primo-vessels are difficult to view under a microscope due to their small diameters (20-50 µm) and translucent appearance. Primo-vessels have a porous outer membrane that encapsulates small channels named Primo sub-vessels filled with flowing fluid. Primo-vessels are classified into six sub-types based on their anatomical location. The physiological mechanisms of Primo-vessel function are not clear. There are multiple hypotheses based on Primo-vessel and Primo-node structure and cell content, however, supportive functional experimental data is lacking. This review focuses on the "interior" lymphatic vessel Primo-vessel (ILVPV) sub-type, the techniques that are used to visualize them, and experimental studies that attempt to unravel their physiological role after inflammatory stimulation. Speculative hypotheses are presented regarding the handling of signals by ILVPVs for intercellular communication between injured cells and cells stored within "interior" lymphatic vessel Primo-nodes (ILVPNs). One of the stored cell types that are of interest for tissue repair are very small embryonic-like cells. Very small embryonic-like cell activation may be induced by biophoton signals emitted by injured cells and transmitted to ILVPNs via Primo-vessel and/or ILVPV networks. An alternative or additional method for intercellular communication may involve the release of signaling proteins and/or extravesicular bodies carrying genetic messages (i.e., exosomes) by cells in injured tissues. As these signaling factors enter the lymphatic circulation, porous ILVPVs filter them out and transport them to ILVPNs where they initiate very small embryonic-like cell activation to start the tissue regenerative process. Primo Vascular System research will require more physiological functional studies to elucidate the role of ILVPVs and ILVPNs in tissue regeneration. To achieve this goal, future mechanistic studies will need novel biomarkers and animal models.