Bhatnagar Payal, Elhariri Sherreen, Burud Ismail A S, Eid Nabil
Department of Pharmaceutical Technology, School of Pharmacy, IMU University, Kuala Lumpur 57000, Malaysia.
Department of Surgery, IMU University, Clinical Campus, Seremban 70300, Negeri Sembilan, Malaysia.
World J Gastroenterol. 2025 Mar 7;31(9):100221. doi: 10.3748/wjg.v31.i9.100221.
Perianal fistulizing Crohn's disease (PFCD) is a common presentation of CD, which affects the patients' quality of life, including social and sexual function. The management of PFCD remains a critical challenge in inflammatory bowel disease, primarily due to limited understanding of the mechanisms involved in its pathogenesis, complicating medical treatment. Increased production of inflammatory cytokines such as tumor necrosis factor and interleukin-13 by infiltrating macrophages and other inflammatory cells stimulate the epithelial-to-mesenchymal transition, resulting in activation of myofibroblasts and elevation of matrix metalloproteinases, leading to fistula formation. Given the potential for malignant transformation, PFCD screening is critical. Cytokine and inflammation-targeted therapies can help control this disease, but recurrence is a common complication. Surgical interventions such as fistulotomy represent viable therapeutic options, with magnetic resonance imaging serving as an important diagnostic tool for delineating fistula tract anatomy. Animal models and clinical trials demonstrate that injection of mesenchymal stem cells (MSCs) into the fistula results in suppression of the inflammatory cells and cytokines and complete resolution of PFCD. Recently, MSC-derived extracellular vesicles were found to stimulate fistula healing, with encouraging results. In this article, we comment on the review article by Pacheco , summarizing the various lines of PFCD treatment and highlighting the role of screening for this disease. Importantly, we focus on the various mechanisms involved in the pathogenesis of PFCD, the therapeutic roles of MSCs and related extracellular vesicles, and explore the potential role of autophagy in enhancing the therapeutic efficacy of these cells, which may help in the treatment of this disease.
肛周瘘管型克罗恩病（PFCD）是克罗恩病的常见表现形式，会影响患者的生活质量，包括社交和性功能。PFCD的治疗仍是炎症性肠病面临的一项严峻挑战，主要原因是对其发病机制所涉及的机制了解有限，使药物治疗变得复杂。浸润的巨噬细胞和其他炎症细胞产生的肿瘤坏死因子和白细胞介素-13等炎症细胞因子增加，刺激上皮-间质转化，导致肌成纤维细胞活化和基质金属蛋白酶升高，从而形成瘘管。鉴于存在恶性转化的可能性，PFCD筛查至关重要。针对细胞因子和炎症的疗法有助于控制这种疾病，但复发是常见的并发症。诸如瘘管切开术等手术干预是可行的治疗选择，磁共振成像作为描绘瘘管解剖结构的重要诊断工具。动物模型和临床试验表明，将间充质干细胞（MSCs）注入瘘管可抑制炎症细胞和细胞因子，并使PFCD完全消退。最近，发现源自MSCs的细胞外囊泡可促进瘘管愈合，结果令人鼓舞。在本文中，我们对Pacheco的综述文章进行评论，总结PFCD的各种治疗方法，并强调该病筛查的作用。重要的是，我们关注PFCD发病机制中涉及的各种机制、MSCs及相关细胞外囊泡的治疗作用，并探讨自噬在增强这些细胞治疗效果方面的潜在作用，这可能有助于治疗这种疾病。
