The advanced 3D lymphatic system for assaying the human cutaneous lymphangiogenesis in the microfluidic platform

Abstract The human cutaneous lymphatic system strictly controls the lymphatic functions as coordinating with skin cells. The lymphatic system plays important roles in removing cell waste, residual proteins, various antigens, and immune cells from tissues in order to maintain homeostasis and activate the immune system, through the drainage of interstitial fluid 1,2. The skin protects our body from external stimulates such as pathogens through the cutaneous lymphatic system 3,4. Herein, to develop the in vitro human cutaneous lymphatic model, we present two 3D microfluidic platforms: a lymphangiogenesis model with a pre-collecting lymphatic vessel-like structure and an advanced lymphangiogenesis model with a functional cutaneous barrier and a pre-collecting lymphatic vessel-like structure. In addition, we rapidly analyzed pro-lymphangiogenesis effects using methods which incorporate a high-speed image processing system and a deep learning-based vascular network analysis algorithm by 12 indices. Using these platforms, we evaluated the pro-lymphangiogenic effect of Lymphanax, a natural product derived from fresh ginseng. As a result, we demonstrated that Lymphanax induces robust lymphangiogenesis without any structural abnormalities. In conclusion, we suggest that these innovative platforms are useful for studying the interaction between the skin and lymphatic system as well as evaluating the pro-lymphangiogenic effects of drugs and cosmetics.