New frontiers of lymphangiogenesis

The history of the lymphatic system includes several scientists who contributed to the discovery of this network. In early times, only macroscopic components of the lymphatic system were described, including lymph nodes and lacteals. After Vesalius’ revolution, new observations were accumulated, and the 17th century is considered the golden age for the investigation of the lymphatic system. In the Enlightenment century, Ruysch described the lymphatic valves, and Mascagni provided a complete iconography of the human lymphatic network. In recent times, different methods to visualize lymphatics were designed and new concepts developed. The concept of lymphosome concerns the skin superficial lymphatic territory. The concept of lymphangion refers to the muscular lymphatic segment between two valves, which behaves like a pump that drives the transport of the lymph. More recently, several lymphatic growth factor/receptor systems were discovered. Two theories of lymphatic vessel development were proposed. The centrifugal theory suggested that lymphatic endothelium was derived by sprouting from venous endothelium. The centripetal theory suggested that lymphatic endothelium differentiates in situ from primitive mesenchyme and secondarily acquires connection with the vascular system. Apart from advances in molecular biology, gross anatomy discoveries still occur. In this respect, in the central nervous system, where the concept of lymphatics absence resists, a paravascular space was described and termed glymphatic (glial-lymphatic) pathway. New data provided evidence that Schlemm’s canal is a component of the lymphatic vascular network, with a unique profile. Another important issue is represented by the progress of medical techniques and devices. © 2026 Elsevier Inc. All rights reserved.