Julia Bukowiecki1, Dominik Pförringer2, Dominik Thor3,4, Dominik Duscher1,4,5,6, Elizabeth Brett7,8. 1. Department of Plastic and Hand Surgery, Technical University of Munich, Munich, Germany. 2. Department of Traumatology, Technical University of Munich, Munich, Germany. 3. College of Pharmacy, University of Florida, Gainesville, Florida, USA. 4. Tomorrowlabs GmbH, Wien, Austria. 5. Section of Plastic Surgery, Kepler University Hospital, Linz, Austria. 6. Department of Plastic, Reconstructive, Hand and Burn Surgery, BG-Trauma Center, Eberhard Karls University Tübingen, Tübingen, Germany. 7. Department of Plastic and Hand Surgery, Technical University of Munich, Munich, Germany, eliza.brett@tum.de. 8. Department of Plastic, Reconstructive, Hand and Burn Surgery, BG-Trauma Center, Eberhard Karls University Tübingen, Tübingen, Germany, eliza.brett@tum.de.
Abstract
INTRODUCTION: Androgenic alopecia (AGA) occurs due to progressive miniaturization of the dermal papilla (DP). During this process the hair follicle loses nutrition over time and eventually dies, causing the hair to fall out. Recent evidence suggests that hypoxia-inducible factor-1a (HIF-1α) modulation may counteract hair loss. This study aims to evaluate the proliferation of dermal papilla cells (DPCs) under the influence of a selection of commercially available topical hair loss drugs, compared to HIF-1α-stimulating agents. MATERIALS AND METHODS: Using the hanging drop method, DPCs self-organized into spheroid shape, mirroring the three-dimensional (3D) structure of the DP in vivo. DP analogs were treated with established substances against AGA (minoxidil and caffeine) compared to HIF-1α-stimulating agents (deferoxamine [DFO] and deferiprone [DFP]), at 10 mM doses. DP analogs were simultaneously stained with 5-bromo-2'-deoxyuridine (BrdU) to evaluate impact of drug compounds on DP daughter cell production. Concurrently, fluorescent microscopy visualization of migration of daughter cells after 48 h in culture was performed. RESULTS: DPC proliferation within the spheroid structure was significantly enhanced by caffeine, minoxidil, and the HIF-1α-stimulating agent DFP when compared to control. Highest proliferation was seen in the DFP-treated DP analogs. Migration of peripheral DP daughter cells was highest in control and DFO groups. CONCLUSION: Here we demonstrate a significantly enhanced proliferative activity for both established substances against AGA (minoxidil and caffeine) and the HIF-1α-stimulating agent DFP in a 3D DPC spheroid culture model with equal results for DFP and minoxidil. These favorable characteristics make such compounds potential water-soluble alternatives to minoxidil.
INTRODUCTION: Androgenic alopecia (AGA) occurs due to progressive miniaturization of the dermal papilla (DP). During this process the hair follicle loses nutrition over time and eventually dies, causing the hair to fall out. Recent evidence suggests that hypoxia-inducible factor-1a (HIF-1α) modulation may counteract hair loss. This study aims to evaluate the proliferation of dermal papilla cells (DPCs) under the influence of a selection of commercially available topical hair loss drugs, compared to HIF-1α-stimulating agents. MATERIALS AND METHODS: Using the hanging drop method, DPCs self-organized into spheroid shape, mirroring the three-dimensional (3D) structure of the DP in vivo. DP analogs were treated with established substances against AGA (minoxidil and caffeine) compared to HIF-1α-stimulating agents (deferoxamine [DFO] and deferiprone [DFP]), at 10 mM doses. DP analogs were simultaneously stained with 5-bromo-2'-deoxyuridine (BrdU) to evaluate impact of drug compounds on DP daughter cell production. Concurrently, fluorescent microscopy visualization of migration of daughter cells after 48 h in culture was performed. RESULTS:DPC proliferation within the spheroid structure was significantly enhanced by caffeine, minoxidil, and the HIF-1α-stimulating agent DFP when compared to control. Highest proliferation was seen in the DFP-treated DP analogs. Migration of peripheral DP daughter cells was highest in control and DFO groups. CONCLUSION: Here we demonstrate a significantly enhanced proliferative activity for both established substances against AGA (minoxidil and caffeine) and the HIF-1α-stimulating agent DFP in a 3D DPC spheroid culture model with equal results for DFP and minoxidil. These favorable characteristics make such compounds potential water-soluble alternatives to minoxidil.