Komulainen Tuomas, Daymond Patrik, Hietanen Kristiina E, Kaartinen Ilkka S, Järvinen Tero A H
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Department of Musculoskeletal Surgery and Diseases, Tampere University Hospital, Tampere, Finland.
Front Med (Lausanne). 2024 Mar 1;11:1293028. doi: 10.3389/fmed.2024.1293028. eCollection 2024.
Keloids form as a pathological response to skin wound healing, and their etiopathology is poorly understood. Myofibroblasts, which are cells transformed from normal fibroblasts, are believed to contribute to pathological scar formation in wounds.
We carried out a double-blinded randomized controlled trial (RCT) comparing the efficacy of intralesional 5-fluorouracil (5-FU) and triamcinolone (TAC) injections in treating keloids. A total of 43 patients with 50 keloids were treated with either intralesional TAC or 5-FU injections, and their clinical response was evaluated. Biopsies were collected before, during, and after injection therapy from the active border of a keloid. To understand the role of myofibroblasts in keloids, we conducted an immunohistochemical analysis to identify myofibroblasts [α-smooth muscle actin (αSMA)] from the biopsies. We first defined the three histologically distinct regions-superficial, middle, and deep dermis-in each keloid.
We then demonstrated that myofibroblasts almost exclusively exist in the middle dermis of the keloids as 80% of the cells in the middle dermis were αSMA positive. However, both the percentage of myofibroblasts as well as the area covered by them was substantially lower in the superficial and deep dermis than in the middle dermis of the keloids. Myofibroblasts do not predict the clinical response to intralesional injection therapies. There is no difference in the myofibroblast numbers in keloids or in the induced change in myofibroblasts between the responders and non-responders after treatment.
This study demonstrates that myofibroblasts reside almost exclusively in the middle dermis layer of the keloids, but their numbers do not predict the clinical response to intralesional injection therapies in the RCT.
瘢痕疙瘩是皮肤伤口愈合的一种病理反应，其发病机制尚不清楚。肌成纤维细胞由正常成纤维细胞转化而来，被认为在伤口病理性瘢痕形成中起作用。
我们进行了一项双盲随机对照试验（RCT），比较病灶内注射5-氟尿嘧啶（5-FU）和曲安奈德（TAC）治疗瘢痕疙瘩的疗效。43例患者的50个瘢痕疙瘩接受了病灶内TAC或5-FU注射治疗，并评估了其临床反应。在注射治疗前、治疗期间和治疗后，从瘢痕疙瘩的活跃边缘采集活检样本。为了解肌成纤维细胞在瘢痕疙瘩中的作用，我们进行了免疫组织化学分析，以从活检样本中鉴定肌成纤维细胞[α-平滑肌肌动蛋白（αSMA）]。我们首先在每个瘢痕疙瘩中定义了三个组织学上不同的区域——浅表真皮、中间真皮和深部真皮。
然后我们证明，肌成纤维细胞几乎只存在于瘢痕疙瘩的中间真皮层，因为中间真皮层中80%的细胞αSMA呈阳性。然而，浅表真皮和深部真皮中的肌成纤维细胞百分比及其覆盖面积均明显低于瘢痕疙瘩中间真皮层。肌成纤维细胞不能预测病灶内注射治疗的临床反应。治疗后，反应者和无反应者的瘢痕疙瘩中肌成纤维细胞数量或肌成纤维细胞的诱导变化没有差异。
本研究表明，肌成纤维细胞几乎只存在于瘢痕疙瘩的中间真皮层，但在RCT中，其数量不能预测病灶内注射治疗的临床反应。
