Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Division of Dermatology, Chulaporn International College of Medicine, Thammasat University, Pathum Thani, Thailand.
J Cosmet Dermatol. 2024 Oct;23(10):3189-3194. doi: 10.1111/jocd.16406. Epub 2024 Jun 19.
Botulinum toxin A (BoNT-A) is widely utilized in the management of hypertrophic and keloid scars. One proposed mechanism for scar prevention involves the inhibition of fibroblast migration in scars by BoNT-A. However, the data regarding the effect of BoNT-A on the migration of normal human dermal fibroblasts (NHDF) is limited.
The aim of this study was to investigate the inhibitory effect of different types and dilutions of BoNT-A on the migration of NHDF.
In vitro scratch wound assay, NHDF cells were cultured, incubated, and subjected to scratching using a sterile tip. Subsequently, the scratched NHDF monolayer was treated with different types of BoNT-A, including onabotulinumtoxinA (ONA), incobotulinumtoxinA (INCO), prabotulinumtoxinA (PRABO), or letibotulinumtoxinA (LETI), at varying concentrations of 10, 20, 25, 40, 50, and 100 units/milliliter (U/mL). Additionally, abobotulinumtoxinA (ABO) was administered at concentrations of 33, 50, 66, 71, 100, 150, 300, and 500 U/mL. Normal saline solution (NSS) served as a negative control. The extent of NHDF migration was evaluated by comparing each dilution of BoNT-A with the controls using high-content imaging at the 48-h time point. Furthermore, the viability of the of NHDF was assessed.
The concentrations of 25, 40, and 50 U/mL of ONA (p < 0.001) and 25 U/mL of LETI (p < 0.05) demonstrated significantly inhibited NHDF migration in comparison to the control group. Conversely, all dilutions of PRABO, INCO, and ABO exhibited comparable NHDF migration to that of the control group. Regarding NHDF viability, no significant decrease was observed across any of the BoNT-A types and dilutions.
Different types and dilutions of BoNT-A demonstrated variable inhibitory effects on NHDF migration in vitro. The selection of BoNT-A formulation may significantly impact the clinical outcome of scar prevention related to fibroblast migration.
肉毒毒素 A（BoNT-A）广泛用于治疗肥厚性瘢痕和瘢痕疙瘩。预防瘢痕的一种机制涉及通过 BoNT-A 抑制瘢痕中的成纤维细胞迁移。然而，关于 BoNT-A 对正常人类真皮成纤维细胞（NHDF）迁移的影响的数据有限。
本研究旨在探讨不同类型和稀释度的 BoNT-A 对 NHDF 迁移的抑制作用。
体外划痕实验，培养 NHDF 细胞，孵育，用无菌尖端划痕 NHDF 单层。随后，用不同类型的 BoNT-A（包括肉毒毒素 A 型[ONA]、依库毒素 A 型[INCO]、帕罗毒素 A 型[PRABO]或利妥昔毒素 A 型[LETI]）以 10、20、25、40、50 和 100 单位/毫升（U/mL）的不同浓度处理划痕 NHDF 单层。此外，用 33、50、66、71、100、150、300 和 500 U/mL 的 abobotulinumtoxinA（ABO）处理。生理盐水溶液（NSS）作为阴性对照。在 48 小时时间点，通过高内涵成像比较 BoNT-A 的每个稀释度与对照，评估 NHDF 迁移的程度。此外，还评估了 NHDF 的活力。
与对照组相比，25、40 和 50 U/mL 的 ONA（p<0.001）和 25 U/mL 的 LETI（p<0.05）浓度显著抑制 NHDF 迁移。相反，PRABO、INCO 和 ABO 的所有稀释度均表现出与对照组相似的 NHDF 迁移。关于 NHDF 活力，没有观察到任何 BoNT-A 类型和稀释度的显著降低。
不同类型和稀释度的 BoNT-A 对 NHDF 的体外迁移表现出不同的抑制作用。BoNT-A 制剂的选择可能会显著影响与成纤维细胞迁移相关的瘢痕预防的临床效果。
