Abstract
Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers. To resemble the in vivo situation as close as possible, we applied the hanging drop cultivation technology regaining most of the markers when cultured in its natural spherical environment. To compare the organotypic 3D sweat gland model versus human sweat glands in vivo, we compared markers relevant for the eccrine sweat gland using transcriptomic and proteomic analysis. Comparing the marker profile, a high in vitro-in vivo correlation was shown. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), muscarinic acetylcholine receptor M3 (CHRM3), Na+-K+-Cl- cotransporter 1 (NKCC1), calcium-activated chloride channel anoctamin-1 (ANO1/TMEM16A), and aquaporin-5 (AQP5) are found at significant expression levels in the 3D model. Moreover, cholinergic stimulation with acetylcholine or pilocarpine leads to calcium influx monitored in a calcium flux assay. Cholinergic stimulation cannot be achieved with the sweat gland cell line NCL-SG3 used as a sweat gland model system. Our results show clear benefits of the organotypic 3D sweat gland model versus 2D cultures in terms of the expression of essential eccrine sweat gland key regulators and in the physiological response to stimulation. Taken together, this novel organotypic 3D sweat gland model shows a good in vitro-in vivo correlation and is an appropriate alternative for screening of potential bioactives regulating the sweat mechanism.
Highlights
Eccrine sweat glands have the major function in regulating human body temperature via evaporation of sweat [1]
The morphological and histochemical analysis of this novel scaffold-free 3D sweat glands (SG) model was determined in bright-field microscopy, by hematoxylin and eosin staining (H&E), and azan staining of paraffin sections of skin tissue and of the 3D SG model (Fig 1)
Eccrine sweat glands maintain body temperature [1], secrete antimicrobial peptides, contribute to skin homeostasis [2,3,4,5,6] and harbor progenitor stem cells involved in wound healing of the human skin [7,8,9,10]
Summary
Eccrine sweat glands have the major function in regulating human body temperature via evaporation of sweat [1]. Besides that, they are involved in skin homeostasis, skin hydration and immune defense by secreting moisturizing factors such as lactate and urea [2] and several. A novel organotypic 3D sweat gland model of salaries and in form of research materials, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the author contributions section
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