Department of Plastic and Hand Surgery, Technical University of Munich, Munich, Germany.
Department of Traumatology, Technical University of Munich, Munich, Germany.
Skin Pharmacol Physiol. 2020;33(6):309-316. doi: 10.1159/000512123. Epub 2020 Dec 16.
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.
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.
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.
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.
雄激素性脱发（AGA）是由于真皮乳头（DP）的进行性微小化引起的。在这个过程中，毛囊随着时间的推移失去营养，最终死亡，导致头发脱落。最近的证据表明，缺氧诱导因子-1a（HIF-1α）的调节可能对抗脱发。本研究旨在评估一系列市售外用脱发药物对真皮乳头细胞（DPC）增殖的影响，并与 HIF-1α 刺激剂进行比较。
使用悬滴法，DPC 自行组织成球体形状，模拟体内 DP 的三维（3D）结构。将 DP 模拟物用现有的 AGA 治疗药物（米诺地尔和咖啡因）处理，与 HIF-1α 刺激剂（去铁胺[DFO]和去铁酮[DFP]）进行比较，剂量为 10mM。DP 模拟物同时用 5-溴-2'-脱氧尿苷（BrdU）染色，以评估药物化合物对 DP 子细胞产生的影响。同时，在培养 48 小时后进行荧光显微镜观察子细胞的迁移。
与对照组相比，咖啡因、米诺地尔和 HIF-1α 刺激剂 DFP 均显著增强了球体结构中 DPC 的增殖。DFP 处理的 DP 模拟物的增殖率最高。在对照组和 DFO 组中，外周 DP 子细胞的迁移率最高。
我们在 3D DPC 球体培养模型中证明了两种已确立的 AGA 治疗药物（米诺地尔和咖啡因）和 HIF-1α 刺激剂 DFP 的显著增强的增殖活性，DFP 和米诺地尔的结果相同。这些有利的特性使这些化合物成为潜在的水溶性米诺地尔替代品。
