An advanced 3D lymphatic system for assaying human cutaneous lymphangiogenesis in a microfluidic platform

Abstract

The human cutaneous lymphatic system strictly controls lymphatic functions by coordinating with skin cells. The lymphatic system plays important roles in removing cell waste, residual proteins, various antigens, and immune cells from tissues to maintain homeostasis and activate the immune system through the drainage of interstitial fluid1,2. The skin protects our body from external stimuli such as pathogens through the cutaneous lymphatic system3,4. Herein, to develop an in vitro human cutaneous lymphatic model, we present two 3D microfluidic platforms: a lymphangiogenesis model with a precollecting lymphatic vessel-like structure and an advanced lymphangiogenesis model with a functional cutaneous barrier and a precollecting lymphatic vessel-like structure. In addition, we rapidly analyzed prolymphangiogenic effects using methods that 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 prolymphangiogenic effects of drugs and cosmetics. The lymphatic system, crucial for maintaining our body's equilibrium by eliminating waste and surplus fluid from tissues, is complex to understand, especially under unusual conditions like inflammation or tumor growth. To aid in this, researchers created a microfluidic chip model (a miniature device that simulates bodily functions) to examine lymphangiogenesis (the creation of new lymphatic vessels) in a regulated setting. This model lets scientists explore how a natural substance, Lymphanax, derived from the root of Panax Ginseng (a type of plant), impacts lymphangiogenesis. The study discovered that Lymphanax encourages the growth of new lymphatic vessels without inducing structural abnormalities, hinting at its potential medicinal value. This investigation paves the way for future study of the lymphatic system and potential treatment trials. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author. The lymphatic system is essential for maintaining homeostasis of our body. Understanding the impact of environmental factors on the lymphatic system and regulating its condition are therefore crucial. We developed a microfluidic device culturing functional skin barrier and lymphatic vessel monolayer. A deep-learning algorithm was employed to validate the pro-lymphangiogenic character of a natural substance Lymphanax (TM), an extract of Panax Ginseng root. We foresee this platform functioning as a valuable research tool for the pharmaceutical and cosmetic industries, replacing the need for animal models.